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Anticancerous Plant Compounds Affecting the Power House of Cancerous Cells: A Possible Herbal Mitocan

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Anticancer Plants: Mechanisms and Molecular Interactions

Abstract

Mitochondria are semiautonomous organelles that play an essential role in cellular metabolism and programmed cell death pathways. Emerging evidences suggest that cancer cells exhibit various degrees of mitochondrial dysfunctions and metabolic alterations. Some of those alterations may provide a selective advantage to cells, allowing them to survive and grow under different stresses. Transformed cells have a very different metabolic and mitochondrial function from their normal counterparts. This is the reason that mitochondrial alterations in cancer cells can offer a great opportunity for efficient and selective anticancer therapy. The mechanism of action of mitochondria-targeted anticancer drugs relies on their ability to disrupt the energy-producing systems of cancer cell, mitochondria leading to increased reactive oxygen species, and activation of the mitochondrial-dependent cell death signaling pathways inside cancer cells. This emerging class of drugs is called as mitocans that affect the activities related to mitochondria, such as hexokinase inhibition, electron transport/respiratory chain blockage, activation of the mitochondrial membrane permeability transition pore targeting constituent protein subunits, and inhibition of Bcl-2 anti-apoptotic family proteins and Bax/Bid pro-apoptotic mimetic. A great deal of pharmaceutical research and refinement in the isolation and structure elucidation techniques has been able to identify various anticancer herbs. Many of these herbs are recognized for their valuable bioactive anticancer compounds. A great progress has been further made to identify the role of these active compounds on targeting mitochondria for cancer treatment. The present chapter described the various natural compounds such as curcumin, capsaicin, berberine, sanguinarine, and lamellarin D, which preferentially target the cancer cells by hindering the mitochondrial function via different mechanisms as “herbal mitocans” and also lowering the side effects of other synthetic anticancer drugs in the treatment of cancer.

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References

  • Achanta G, Sasaki R, Feng L, Carew JS, Lu W, Pelicano H, Keating MJ, Huang P (2005) Novel role of p53 in maintaining mitochondrial genetic stability through interaction with DNA Pol gamma. EMBO J 24:3482–3492

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Adam-Vizi V, Chinopoulos C (2006) Bioenergetics and the formation of mitochondrial reactive oxygen species. Trends Pharmacol Sci 27:639–645

    Article  PubMed  CAS  Google Scholar 

  • Antico Arciuch VG, Elguero ME, Poderoso JJ, Carreras MC (2012) Mitochondrial regulation of cell cycle and proliferation. Antioxid Redox Signal 16:1150–1180

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Aoganghua A, Nishiumi S, Kobayashi K, Nishida M, Kuramochi K, Tsubaki K, Hirai M, Tanaka S, Azuma T, Yoshida H, Mizushina Y, Yoshida M (2011) Inhibitory effects of vitamin K3 derivatives on DNA polymerase and inflammatory activity. Int J Mol Med 28:937–945

    PubMed  CAS  Google Scholar 

  • Azevedo-Silva J, Queirós O, Ribeiro A, Baltazar F, Young KH, Pedersen PL, Preto A, Casal M (2015) The cytotoxicity of 3-bromopyruvate in breast cancer cells depends on extracellular pH. Biochem J 467:247–258

    Article  PubMed  CAS  Google Scholar 

  • Baggetto LG, Testa-Parussini R (1990) Role of acetoin on the regulation of intermediate metabolism of Ehrlich ascites tumor mitochondria: its contribution to membrane cholesterol enrichment modifying passive proton permeability. Arch Biochem Biophys 283:241–248

    Article  PubMed  CAS  Google Scholar 

  • Bajpai P, Sangar MC, Singh S, Tang W, Bansal S, Chowdhury G, Cheng Q, Ji-Kang F, Martin MV, Guengerich FP, Avadhani NG (2012) Metabolism of 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine by mitochondria-targeted cytochrome P450 2D6: implications in Parkinson’s disease. J Biol Chem 288:4436–4451

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Berridge KC (2009) Liking’ and ‘wanting’ food rewards: brain substrates and roles in eating disorders. Physiol Behav 97:537–550

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Bertram R, Pedersen MG, Luciani DS, Sherman A (2006) A simplified model for mitochondrial ATP production. J Theor Biol 243:575–586

    Article  PubMed  CAS  Google Scholar 

  • Birringer M, Eytina JH, Salvatore BA, Neuzil J (2003) Vitamin E analogues as inducers of apoptosis: structure-function relation. Br J Cancer 88:1948–1955

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Bonnet S, Archer SL, Allalunis-Turner J, Haromy A, Beaulieu C, Thompson R, Lee CT, Lopaschuk GD, Puttagunta L, Bonnet S, Harry G, Hashimoto K, Porter CJ, Andrade MA, Thebaud B, Michelakis ED (2007) A mitochondria-K+ channel axis is suppressed in cancer and its normalization promotes apoptosis and inhibits cancer growth. Cancer Cell 11:37–51

    Article  PubMed  CAS  Google Scholar 

  • Brandon M, Baldi PA, Wallace DC (2006) Mitochondrial mutations in cancer. Oncogene 25:4647–4662

    Article  PubMed  CAS  Google Scholar 

  • Brenner C, Lemoine A (2014) Mitochondrial proteins (e.g., VDAC, Bcl-2, HK, ANT) as major control points in oncology. Front Oncol 4:365

    Article  PubMed  PubMed Central  Google Scholar 

  • Bustamante E, Morris HA, Pedersen PL (1981) Energy metabolism of tumor cells. Requirement for a form of hexokinase with a propensity for mitochondrial binding. J Biol Chem 256:8699–8704

    PubMed  CAS  Google Scholar 

  • Cavalieri E, Bergamini C, Mariotto S, Leoni S, Perbellini L, Darra E, Suzuki H, Fato R, Lenaz G (2009) Involvement of mitochondrial permeability transition pore opening in α-bisabolol induced apoptosis. FEBS J 276:3990–4000

    Article  PubMed  CAS  Google Scholar 

  • Chen G, Izzo J, Demizu Y, Wang F, Guha S, Wu X, Hung M, Ajani JA, Huang P (2009a) Different redox states in malignant and nonmalignant esophageal epithelial cells and differential cytotoxic responses to bile acid and honokiol. Antioxid Redox Signal 11:1083–1095

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Chen Z, Zhang H, Lu W, Huang P (2009b) Role of mitochondria-associated hexokinase II in cancer cell death induced by 3-bromopyruvate. Biochim Biophys Acta 1787:553–560

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Chen KG, Valencia JC, Gillet JP, Hearing VJ, Gottesman MM (2009c) Involvement of ABC transporters in melanogenesis and the development of multidrug resistance of melanoma. Pigment Cell Melanoma Res 22:740–749

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Chen V, Staub RE, Fong S, Tagliaferri M, Cohen I, Shtivelman E (2012) Bezielle selectively targets mitochondria of cancer cells to inhibit glycolysis and OXPHOS. PLoS One 7:e30300

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Constance JE, Lim CS (2012) Targeting malignant mitochondria with therapeutic peptides. Ther Deliv 3:961–979

    Article  PubMed  CAS  Google Scholar 

  • Da Silva AP, El-Bacha T, Kyaw N, Dos Santos RS, Da-Silva WS, Almeida FC, Da Poian AT, Galina A (2009) Inhibition of energy-producing pathways of HepG2 cells by 3-bromopyruvate. Biochem J 417:717–726

    Article  CAS  Google Scholar 

  • Dell’Antone P (2009) Targets of 3-bromopyruvate, a new, energy depleting, anticancer agent. Med Chem 5:491–496

    Article  PubMed  Google Scholar 

  • Deng S, Yu B, Lou Y, Hui Y (1999) First total synthesis of an exceptionally potent antitumor saponin, OSW-1. J Org Chem 64:202–208

    Article  PubMed  CAS  Google Scholar 

  • Di Monte D, Ross D, Bellomo G, Eklow L, Orrenius S (1984) Alterations in intracellular thiol homeostasis during the metabolism of menadione by isolated rat hepatocytes. Biochem Pharmacol 41:1283–1292

    Google Scholar 

  • Don AS, Kisker O, Dilda P, Donoghue N, Zhao X, Decollogne S, Creighton B, Flynn E, Folkman J, Hogg PJ (2003) A peptide trivalent arsenical inhibits tumor angiogenesis by perturbing mitochondrial function in angiogenic endothelial cells. Cancer Cell 3:497–509

    Article  PubMed  CAS  Google Scholar 

  • Dong L, Low P, Dyason JC, Wang X, Prochazka L, Witting PK, Freeman R, Swettenham E, Valis K, Liu J, Zobalova R, Turanek J, Spitz DR, Domann FE, Scheffler IE, Ralph SJ, Neuzil J (2008) α-Tocopheryl succinate induces apoptosis by targeting ubiquinone-binding sites in mitochondrial respiratory complex II. Oncogene 27:4324–4335

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Dong LF, Freeman R, Ji L, Neuzil J (2009) Suppression of tumor growth in vivo by the mitocan alpha-tocopheryl succinate requires respiratory complex II. Clin Cancer Res 15:1593–1600

    Google Scholar 

  • Dong LF, Jameson VJ, Tilly D, Cerny J, Mahdavian E, Marín-Hernández A, Hernández-Esquivel L, Rodríguez-Enríquez S, Stursa J, Witting PK, Stantic B, Rohlena J, Truksa J, Kluckova K, Dyason JC, Ledvina M, Salvatore BA, Moreno-Sánchez R, Coster MJ, Ralph SJ, Smith RA, Neuzil J (2011a) Mitochondrial targeting of vitamin E succinate enhances its pro-apoptotic and anti-cancer activity via mitochondrial complex II. J Biol Chem 286:3717–3728

    Article  PubMed  CAS  Google Scholar 

  • Dong LF, Jameson VJA, Tilly D, Prochazka L, Rohlena J, Valis K, Truksa J, Zobalova R, Mahdavian E, Kluckova K, Stantic M, Stursa J, Freeman R, Witting PK, Norberg E, Goodwin J, Salvatore BA, Novotna J, Neuzil J (2011b) Mitochondrial targeting of α-tocopheryl succinate enhances its pro-apoptotic efficacy: a new paradigm of efficient anti-cancer therapy. Free Radic Biol Med 50:1546–1555

    Article  PubMed  CAS  Google Scholar 

  • Drose S (2013) Differential effects of Complex II on mitochondrial ROS production and their relation to cardioprotective pre- and post-conditioning. Biochim Biophys Acta 1827:578–587

    Article  PubMed  CAS  Google Scholar 

  • Ellerby HM, Arap W, Ellerby LM, Kain R, Andrusiak R, Del Rio G, Krajewski S, Lombardo CR, Rao R, Ruoslahti E, Bredese DE, Pasqualini R (1999) Anticancer activity of targeted pro-apoptotic peptides. Nat Med 5:1032–1038

    Article  PubMed  CAS  Google Scholar 

  • Elmore S (2007) Apoptosis: a review of programmed cell death. Toxicol Pathol 35:495–516

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Fan J, Kamphorst JJ, Mathew R, Chung MK, White E, Shlomi T, Rabinowitz JD (2013) Glutamine-driven oxidative phosphorylation is a major ATP source in transformed mammalian cells in both normoxia and hypoxia. Mol Syst Biol 9:712. https://doi.org/10.1038/msb.2013.65

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Fogg VC, Lanning NJ, MacKeigan JP (2011) Mitochondria in cancer: at the crossroads of life and death. Chin J Cancer 30:526–539

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Fried LE, Arbiser JL (2009) Honokiol, a multifunctional antiangiogenic and antitumor agent. Antioxid Redox Signal 11:1139–1148

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Fruehauf JP, Meyskens FL Jr (2007) Reactive oxygen species: a breath of life or death. Clin Cancer Res 13:789–794

    Article  PubMed  CAS  Google Scholar 

  • Fulda S, Kroemer G (2011) Mitochondria as therapeutic targets for the treatment of malignant disease. Antioxid Redox Signal 15:2937–2949

    Article  PubMed  CAS  Google Scholar 

  • Fulda S, Galluzzi L, Kroemer G (2010) Targeting mitochondria for cancer therapy. Nat Rev Drug Discov 9:447–464

    Article  PubMed  CAS  Google Scholar 

  • Galluzzi L, Morselli E, Kepp O, Tajeddine N, Kroemer G (2008) Targeting p53 to mitochondria for cancer therapy. Cell Cycle 7:1949–1955

    Article  PubMed  CAS  Google Scholar 

  • Galluzzi L, Morselli E, Kepp O, Vitale I, Rigoni A, Vacchelli E, Michaud M, Zischka H, Castedo M, Kroemer G (2010) Mitochondrial gateways to cancer. Mol Asp Med 31:1–20

    Article  CAS  Google Scholar 

  • Gerlinger M, Rowan AJ, Horswell S, Math M, Larkin J, Endesfelder D, Gronroos E, Martinez P, Matthews N, Stewart A, Tarpey P, Varela I, Phillimore B, Begum S, McDonald NQ, Butler A, Jones D, Raine K, Latimer C, Santos CR, Nohadani M, Eklund AC, Spencer-Dene B, Clark G, Pickering L, Stamp G, Gore M, Szallasi Z, Downward J, Futreal PA, Swanton C (2012) Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med 366:883–892

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Gibellini L, Bianchini E, De Biasi S, Nasi M, Cossarizza A, Pinti M (2015) Natural compounds modulating mitochondrial functions. Evid Based Complement Alternat Med 2015:527209. https://doi.org/10.1155/2015/527209

    Article  PubMed  PubMed Central  Google Scholar 

  • Gogada R, Amadori M, Zhang H, Jones A, Verone A, Pitarresi J, Jandhyam S, Prabhu V, Black JD, Chandra D (2011a) Curcumin induces Apaf-1-dependent, p21-mediated caspase activation and apoptosis. Cell Cycle 10:4128–4137

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Gogada R, Prabhu V, Amadori M, Scott R, Hashmi S, Chandra D (2011b) Resveratrol induces p53-independent, X-linked inhibitor of apoptosis protein (XIAP)-mediated Bax protein oligomerization on mitochondria to initiate cytochrome c release and caspase activation. J Biol Chem 286:28749–28760

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Gold J (1986) In vivo synergy of vitamin K3 and methotrexate in tumor-bearing animals. Cancer Treat Rep 70:1433–1435

    PubMed  CAS  Google Scholar 

  • Gottlieb E, Tomlinson IP (2005) Mitochondrial tumour suppressors: a genetic and biochemical update. Nat Rev Cancer 5:857

    Article  PubMed  CAS  Google Scholar 

  • Guzy RD, Schumacker PT (2006) Oxygen sensing by mitochondria at Complex III: the paradox of increased reactive oxygen species during hypoxia. Exp Physiol 91:807–819

    Article  PubMed  CAS  Google Scholar 

  • Halestrap AP (2009) What is the mitochondrial permeability transition pore. J Mol Cell Cardiol 46:821–831

    Article  PubMed  CAS  Google Scholar 

  • Hatefi Y (1993) ATP synthesis in mitochondria. Eur J Biochem 218:759–767

    Article  PubMed  CAS  Google Scholar 

  • Herbst RS, Onn A, Sandler A (2005) Angiogenesis and lung cancer: prognostic and therapeutic implications. J Clin Oncol 23:3243–3256

    Article  PubMed  CAS  Google Scholar 

  • Higgins MJ, Stearns V (2011) Pharmacogenetics of endocrine therapy for breast cancer. Annu Rev Med 62:281–293

    Article  PubMed  CAS  Google Scholar 

  • Houston MA, Augenlicht LH, Heerdt BG (2011) Stable differences in intrinsic mitochondrial membrane potential of tumor cell subpopulations reflect phenotypic heterogeneity. Int J Cell Biol 2011:978583. https://doi.org/10.1155/2011/978583

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Huang P, Feng L, Oldham EA, Keating MJ, Plunkett W (2000) Superoxide dismutase as a target for the selective killing of cancer cells. Nature 407:390–395

    Article  PubMed  CAS  Google Scholar 

  • Ishitsuka K, Hideshima T, Hamasaki M, Raje N, Kumar S, Hideshima H, Shiraishi N, Yasui H, Roccaro AM, Richardson P, Podar K, Le Gouill S, Chauhan D, Tamura K, Arbiser J, Anderson KC (2005) Honokiol overcomes conventional drug resistance in human multiple myeloma by induction of caspase-dependent and -independent apoptosis. Blood 106:1794–1800

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Jian L, Xie LP, Lee AH, Binns CW (2004) Protective effect of green tea against prostate cancer: a case-control study in southeast China. Int J Cancer 108:130–135

    Article  PubMed  CAS  Google Scholar 

  • Johnson LV, Walsh ML, Chen LB (1980) Localization of mitochondria in living cells with rhodamine 123. Proc Natl Acad Sci 77(2):990–994

    Article  CAS  Google Scholar 

  • Kepp O, Galluzzi L, Lipinski M (2011) Cell death assays for drug discovery. Nat Rev Drug Discov 10:221–237

    Article  PubMed  CAS  Google Scholar 

  • Ko YH, Smith BL, Wang Y, Pomper MG, Rini DA, Torbenson MS, Hullihen J, Pedersen PL (2004) Advanced cancers: eradication in all cases using 3-bromopyruvate therapy to deplete ATP. Biochem Biophys Res Commun 324:269–275

    Article  PubMed  CAS  Google Scholar 

  • Koppenol WH, Bounds PL, Dang CV (2011) Otto Warburg’s contributions to current concepts of cancer metabolism. Nat Rev Cancer 11:325–337

    Article  PubMed  CAS  Google Scholar 

  • Kroemer G (2006) Mitochondria in cancer. Oncogene 25:4630–4632

    Article  PubMed  CAS  Google Scholar 

  • Kroemer G, Galluzzi L, Brenner C (2007) Mitochondrial membrane permeabilization in cell death. Physiol Rev 87:99–163

    Article  PubMed  CAS  Google Scholar 

  • Lampidis TJ, Bernal SD, Summerhayes IC, Chen LB (1983) Selective toxicity of rhodamine 123 in carcinoma cells in vitro. Cancer Res 43:716–720

    PubMed  CAS  Google Scholar 

  • Le SB, Hailer MK, Buhrow S, Wang Q, Flatten K, Pediaditakis P, Bible KC, Lewis LD, Sausville EA, Pang YP, Ames MW, Lemasters JJ, Holmuhamedov E, Kaufmann SH (2007) Inhibition of mitochondrial respiration as a source of adaphostin-induced reactive oxygen species and cytotoxicity. J Biol Chem 282:8860–8872

    Article  PubMed  CAS  Google Scholar 

  • LeBleu VS, O’Connell JT, Gonzalez Herrera KN, Wikman H, Pantel K, Haigis MC, de Carvalho FM, Damascena A, Domingos Chinen LT, Rocha RM, Asara JM, Kalluri R (2014) PGC-1 mediates mitochondrial biogenesis and oxidative phosphorylation to promote metastasis. Nat Cell Biol 16:992–1015

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lee YJ, Shacter E (1999) Oxidative stress inhibits apoptosis in human lymphoma cells. J Biol Chem 274:19792–19798

    Article  PubMed  CAS  Google Scholar 

  • Letašiová S, Jantová S, Múčková M (2006) Berberine-antiproliferative activity in vitro and induction of apoptosis/necrosis of the U937 and B16 cells. Cancer Lett 239:254–262

    Article  PubMed  CAS  Google Scholar 

  • Lewis W, Levine ES, Griniuviene B, Tankersley KO, Colacino JM, Sommadossi JP, Watanabe KA, Perrino FW (1996) Fialuridine and its metabolites inhibit DNA polymerase-γ at sites of multiple adjacent analog incorporation, decrease mtDNA abundance, and cause mitochondrial structural defects in cultured hepatoblasts. Proc Natl Acad Sci U S A 93:3592–3597

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Li L, Han W, Gu Y, Qiu S, Lu Q, Jin J, LuoJ HX (2007) Honokiol induces a necrotic cell death through the mitochondrial permeability transition pore. Cancer Res 67:4894–4903

    Article  PubMed  CAS  Google Scholar 

  • Liu H, Zang C, Emde A, Planas-Silva MD, Rosche M, Kühnl A, Schulz CO, Elstner E, Possinger K, Eucker J (2008) Antitumor effect of honokiol alone and in combination with other anticancer agents in breast cancer. Eur J Pharmacol 591:43–51

    Article  PubMed  CAS  Google Scholar 

  • Ludueña RF, Roach MC, Prasad V, Pettit GR (1992) Interaction of dolastatin 10 with bovine brain tubulin. Biochem Pharmacol 43:539–543

    Article  PubMed  Google Scholar 

  • Ma X, Yu B, Hui Y, Miao Z, Ding J (2001) Synthesis of OSW-1 analogues and a dimer and their antitumor activities. Bioorg Med Chem Lett 11:2153–2156

    Article  PubMed  CAS  Google Scholar 

  • Marino AA, Lliev IG, Gonzalez E, Marter KC, Flanagan CA (1994) Association between cell membrane potential and breat cancer. Tumour Biol 15:82–89

    Article  PubMed  CAS  Google Scholar 

  • Mathupala SP, Ko YH, Pedersen PL (2006) Hexokinase II: cancer’s double-edged sword acting as both facilitator and gatekeeper of malignancy when bound to mitochondria. Oncogene 25:4777–4786

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Matoba S, Kang JG, Patino WD, Wragg A, Boehm M, Gavrilova O, Hurley PJ, Bunz F, Hwang PM (2006) p53 regulates mitochondrial respiration. Science 312:1650–1653

    Article  PubMed  CAS  Google Scholar 

  • Mestre-Escorihuela C, Rubio-Moscardo F, Richter JA, Siebert R, Climent J, Fresquet V, Beltran E, Agirre X, Marugan I, Marín M, Rosenwald A, Sugimoto KJ, Wheat LM, Karran EL, García JF, Sanchez L, Prosper F, Staudt LM, Pinkel D, Dyer MJ, Martinez-Climent JA (2007) Homozygous deletions localize novel tumor suppressor genes in B-cell lymphomas. Blood 109:271–280

    Article  PubMed  CAS  Google Scholar 

  • Miller WH Jr (2002) Molecular targets of arsenic trioxide in malignant cells. Oncologia 1:14–19

    Article  Google Scholar 

  • Miyako K, Kai Y, Irie T, Takeshige K, Kang D (1997) The content of intracellular mitochondrial DNA is decreased by 1-methyl-4-phenylpyridinium ion (MPP+). J Biol Chem 272:9605–9608

    Article  PubMed  CAS  Google Scholar 

  • Miyata T, Takizawa S, van Ypersele de Strihou C (2011) Hypoxia. 1. Intracellular sensors for oxygen and oxidative stress: novel therapeutic targets. Am J Physiol Cell Physiol 300:C226–C231

    Article  PubMed  CAS  Google Scholar 

  • Modica-Napolitano JS, Kulawiec M, Singh KK (2007) Mitochondria and human cancer. Curr Mol Med 7:121–131

    Article  PubMed  CAS  Google Scholar 

  • Moreira PI, Custódio J, Moreno A, Oliveira CR, Santos MS (2006) Tamoxifen and estradiol interact with the flavin mononucleotide site of complex I leading to mitochondrial failure. J Biol Chem 281:10143–10152

    Article  PubMed  CAS  Google Scholar 

  • Moreno-Sánchez R, Saavedra E, Rodríguez-Enríquez S, Gallardo-Pérez JC, Quezada H, Westerhoff HV (2010) Metabolic control analysis indicates a change of strategy in the treatment of cancer. Mitochondrion 10:626–639

    Article  PubMed  CAS  Google Scholar 

  • Munroe ME, Arbiser JL, Bishop GA (2007) Honokiol, a natural plant product, inhibits inflammatory signals and alleviates inflammatory arthritis. J Immunol 179:753–763

    Article  PubMed  CAS  Google Scholar 

  • Murphy MP (2009) How mitochondria produce reactive oxygen species. Biochemist 417:1–13

    Article  CAS  Google Scholar 

  • Nakachi K, Suemasu K, Suga K, Takeo T, Imai K, Higashi Y (1998) Influence of drinking green tea on breast cancer malignancy among Japanese patients. Jpn J Cancer Res 89:254–261

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Nakazato T, Ito K, Ikeda Y, Kizaki M (2005) Green tea component, catechin, induces apoptosis of human malignant B cells via production of reactive oxygen species. Clin Cancer Res 11:6040–6049

    Article  PubMed  CAS  Google Scholar 

  • Neuzil J (2004) Vitamin E analogues: a new class of inducers of apoptosis with selective anti-cancer effect. Curr Cancer Drug Targets 4:267–283

    Article  Google Scholar 

  • Neuzil J, Dong LF, Ramanathapuram L, Hahn T, Chladova M, Wang XF, Zobalova R, Prochazka L, Gold M, Freeman R, Turanek J, Akporiaye ET, Dyason JC, Ralph S (2007) Vitamin E analogues: a novel group of mitocans, anticancer agents that act by targeting mitochondria. Mol Asp Med 28:607–645

    Article  CAS  Google Scholar 

  • Neuzil J, Dong LF, Rohlena J, Truksa J, Ralph SJ (2013) Classification of mitocans, anti-cancer drugs acting on mitochondria. Mitochondrion 13:199–208

    Article  PubMed  CAS  Google Scholar 

  • Nihal M, Ahmad N, Mukhtar H, Wood GS (2005) Anti-proliferative and proapoptotic effects of (-)-epigallocatechin-3-gallate on human melanoma: possible implications for the chemoprevention of melanoma. Int J Cancer 114:513–521

    Article  PubMed  CAS  Google Scholar 

  • Nutter LM, Cheng AL, Hung HL, Hsieh RK, Ngo EO, Liu TW (1991) Menadione: spectrum of anticancer activity and effects on nucleotide metabolism in human neoplastic cell lines. Biochem Pharmacol 41:1283–1292

    Article  PubMed  CAS  Google Scholar 

  • Ogasawara MA, Zhang H (2009) Redox regulation and its emerging roles in stem cells and stem-like cancer cells. Antioxid Redox Signal 11:1107–1122

    Article  PubMed  CAS  Google Scholar 

  • Oliver CL, Miranda MB, Shangary S, Land S, Wang S, Johnson DE (2005) Gossypol acts directly on the mitochondria to overcome Bcl-2- and Bcl-xL-mediated apoptosis resistance. Mol Cancer Ther 4:23–31

    Article  PubMed  CAS  Google Scholar 

  • Ott M, Gogvadze V, Orrenius S, Zhivotovsky B (2007) Mitochondria, oxidative stress and cell death. Apoptosis 12:913–922

    Article  PubMed  CAS  Google Scholar 

  • Pandey S, Kekre N, Naderi J, McNulty J (2005) Induction of apoptotic cell death specifically in rat and human cancer cells by pancratistatin. Artif Cells Blood Substit Immobil Biotechnol 33:279–295

    Article  PubMed  CAS  Google Scholar 

  • Pani G, Koch OR, Galeotti T (2009) The p53-p66shc-manganese superoxide dismutase (MnSOD) network: a mitochondrial intrigue to generate reactive oxygen species. Int J Biochem Cell Biol 41:1002–1005

    Article  PubMed  CAS  Google Scholar 

  • Paul TS (2011) Lung cell hypoxia role of mitochondrial reactive oxygen species signaling in triggering responses. Proc Am Thorac Soc 8:477–484

    Article  CAS  Google Scholar 

  • Pedersen PL (1978) Tumor mitochondria and the bioenergetics of cancer cells. Prog Exp Tumor Res 22:190–274

    Article  PubMed  CAS  Google Scholar 

  • Pelicano H, Feng L, Zhou Y, Carew JS, Hileman EO, Plunkett W, Keating MJ, Huang P (2003) Inhibition of mitochondrial respiration: a novel strategy to enhance druginduced apoptosis in human leukemia cells by a reactive oxygen species-mediated mechanism. J Biol Chem 278:37832–37839

    Article  PubMed  CAS  Google Scholar 

  • Pelicano H, Martin DS, Xu RH, Huang P (2006) Glycolysis inhibition for anticancer treatment. Oncogene 25:4633–4646

    Article  PubMed  CAS  Google Scholar 

  • Raffo AJ, Perlman H, Chen MW, Day ML, Streitman JS, Buttyan R (1995) Overexpression of Bcl-2 protects prostate cancer cells from apoptosis in vitro and confers resistance to androgen depletion in vivo. Cancer Res 55:4438–4445

    Google Scholar 

  • Ralph SJ, Neuzil J (2008) Mitochondria as targets for cancer therapy. Mol Nutr Food Res 53:9–28

    Article  CAS  Google Scholar 

  • Ralph SJ, Rodríguez-Enríquez S, Neuzil J, Moreno-Sánchez R (2010a) Bioenergetic pathways in tumor mitochondria as targets for cancer therapy and the importance of the ROS-induced apoptotic trigger. Mol Asp Med 31:29–59

    Article  CAS  Google Scholar 

  • Ralph SJ, Rodríguez-Enríquez S, Neuzil J, Saavedra E, Moreno-Sánchez R (2010b) The causes of cancer revisited: “mitochondrial malignancy” and ROS-induced oncogenic transformation – why mitochondria are targets for cancer therapy. Mol Asp Med 31:145–170

    Article  CAS  Google Scholar 

  • Ralph SJ, Moreno-Sánchez R, Neuzil J, Rodríguez-Enríquez S (2011) Inhibitors of the succinate: quinine reductase/complex II regulate production of mitochondrial reactive oxygen species and protect normal cells from ischemic damage but induce specific cancer cell death. Pharm Res 28:2695–2730

    Article  PubMed  CAS  Google Scholar 

  • Rose P, Whiteman M, Huang SH, Halliwell B, Ong CN (2003) β-Phenylethylisothiocyanate mediated apoptosis in hepatoma HepG2 cells. Cell Mol Life Sci 60:1489–1503

    Article  PubMed  CAS  Google Scholar 

  • Roy P, Kalra N, Prasad S, George J, Shukla Y (2009) Chemopreventive potential of resveratrol in mouse skin tumors through regulation of mitochondrial and PI3K/AKT signaling pathways. Pharm Res 26:211–217

    Article  PubMed  CAS  Google Scholar 

  • Sasaki R, Suzuki Y, Yonezawa Y (2008) DNA polymerase gamma inhibition by vitamin K3 induces mitochondria-mediated cytotoxicity in human cancer cells. Cancer Sci 99:1040–1048

    Article  PubMed  CAS  Google Scholar 

  • Satyan KS, Swamy N, Dizon DS, Singh R, Granai CO, Brard L (2006) Phenethylisothio cyanate (PEITC) inhibits growth of ovarian cancer cells by inducing apoptosis: role of caspase and MAPK activation. Gynecol Oncol 103:261–270

    Article  PubMed  CAS  Google Scholar 

  • Schagger H, Pfeiffer K (2000) Supercomplexes in the respiratory chains of yeast and mammalian mitochondria. EMBO J 19:1777–1783

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Schroeder EK, Kelsey NA, Doyle J, Breed E, Bouchard RJ, Loucks FA, Harbison RA, Linseman DA (2009) Green tea epigallocatechin 3-gallate accumulates in mitochondria and displays a selective antiapoptotic effect against inducers of mitochondrial oxidative stress in neurons. Antioxid Redox Signal 11:469–480

    Article  PubMed  CAS  Google Scholar 

  • Schumacker PT (2006) Reactive oxygen species in cancer cells: live by the sword, die by the sword. Cancer Cell 10:175–176

    Article  PubMed  CAS  Google Scholar 

  • Siedlakowski P, McLachlan-Burgess A, Griffin C, Tirumalai SS, Nulty JM, Pandey S (2008) Synergy of Pancratistatin and Tamoxifen on breast cancer cells in inducing apoptosis by targeting mitochondria. Cancer Biol Ther 7:376–384

    Article  CAS  Google Scholar 

  • Shamasdin A, Kale J, Leber B, Andrews DW (2013) Mechanisms of action of Bcl-2 family proteins. Cold Spring Harb Perspect Biol 5:a008714

    Google Scholar 

  • Shanafelt TD, Lee YK, Call TG, Nowakowski GS, Dingli D, Zent CS, Kay NE (2006) Clinical effects of oral green tea extracts in four patients with low grade B-cell malignancies. Leuk Res 30:707–712

    Article  PubMed  CAS  Google Scholar 

  • Simons AL, Ahmad IM, Mattson DM (2007) 2-Deoxy-Dglucosecombined with cisplatin enhances cytotoxicity via metabolic oxidative stress inhuman head and neck cancer cells. Cancer Res 67:3364–3370

    Article  PubMed  CAS  Google Scholar 

  • Singh S, Khar A (2006) Biological effects of curcumin and its role in cancer chemoprevention and therapy. Anti Cancer Agents Med Chem 6:259–270

    Article  CAS  Google Scholar 

  • Stapelberg M, Gellert N, Swettenham E (2005) α-tocopheryl succinate inhibits malignant mesothelioma by disrupting the fibroblast growth factor autocrine loop mechanism and the role of oxidative stress. J Biol Chem 280:25369–25376

    Article  PubMed  CAS  Google Scholar 

  • Suen DF, Norris KL, Youle RJ (2008) Mitochondrial dynamics and apoptosis. Genes Dev 22:1577–1590

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Sullivan R, Paré GC, Frederiksen LJ, Semenza GL, Graham CH (2008) Hypoxia-induced resistance to anticancer drugs is associated with decreased senescence and requires hypoxia-inducible factor-1 activity. Mol Cancer Ther 7:1961–1973

    Article  PubMed  CAS  Google Scholar 

  • Sun M, Lou W, Chun JY, Cho DS, Nadiminty N, Evans CP, Chen J, Yue J, Zhou Q, Gao AC (2010) Sanguinarine suppresses prostate tumor growth and inhibits survivin expression. Genes Cancer 1:283–292

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Szatrowski TP, Nathan CF (1991) Production of large amounts of hydrogen peroxide by human tumor cells. Cancer Res 51:794–798

    PubMed  CAS  Google Scholar 

  • Talari M, Seydi E, Salimi A, Mohsenifar Z, Kamalinejad M, Pourahmad J (2014) Dracocephalum: novel anticancer plant acting on liver cancer cell mitochondria. Biomed Res Int 2014:892170. https://doi.org/10.1155/2014/892170

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Tan AS, Baty JW, Dong LF, Bezawork-Geleta A, Endaya B, Goodwin J, Bajzikova M, Kovarova J, Peterka M, Yan B, Pesdar EA, Sobol M, Filimonenko A, Stuart S, Vondrusova M, Kluckova K, Sachaphibulkij K, Rohlena J, Hozak P, Truksa J, Eccles D, Haupt LM, Griffiths LR, Neuzil J, Berridge MV (2015) Mitochondrial genome acquisition restores respiratory function and tumorigenic potential of cancer cells without mitochondrial DNA. Cell Metab 21:81–94

    Article  PubMed  CAS  Google Scholar 

  • Terwilliger T, Abdul-Hay M (2017) Acute lymphoblastic leukemia: a comprehensive review and 2017 update. Blood Cancer J 7:e577

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Trachootham D, Zhou Y, Zhang H, Demizu Y, Chen Z, Pelicano H, Chiao PJ, Achanta G, Arlinghaus RB, Liu J, Huang P (2006) Selective killing of oncogenically transformed cells through a ROS-mediated mechanism by beta-phenylethylisothiocyanate. Cancer Cell 10:241–252

    Article  PubMed  CAS  Google Scholar 

  • Trachootham D, Lu W, Ogasawara MA, Nilsa RD, Huang P (2008a) Redox regulation of cell survival. Antioxid Redox Signal 10:1343–1374

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Trachootham D, Zhang H, Zhang W, Feng L, Du M, Zhou Y, Chen Z, Pelicano H, Plunkett W, Wierda WG, Keating MJ, Huang P (2008b) Effective elimination of fludarabine-resistant CLL cells by PEITC through a redox-mediated mechanism. Blood 112:1912–1922

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Trachootham D, Alexandre J, Huang P (2009) Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach. Nat Rev Drug Discov 8:579–591

    Article  PubMed  CAS  Google Scholar 

  • Tuorkey MJ (2014) Curcumin a potent cancer preventive agent: mechanisms of cancer cell killing. Interv Med Appl Sci 6:139–146

    PubMed  PubMed Central  Google Scholar 

  • Turánek J, Wang XF, Knötigová P, Koudelka S, Dong LF, Vrublová E, Mahdavian E, Procházka L, Sangsura S, Vacek A, Salvatore BA, Neuzil J (2009) Liposomal formulation of alpha-tocopheryl maleamide: In vitro and in vivo toxicological profile and anticancer effect against spontaneous breast carcinomas in mice. Toxicol Appl Pharmacol 237:249–257

    Article  PubMed  CAS  Google Scholar 

  • Umeda S, Muta T, Ohsato T, Takamatsu C, Hamasaki N, Kang D (2000) The D-loop structure of human mtDNA is destabilized directly by 1-methyl-4-phenylpyridinium ion (MPP+), a parkinsonism-causing toxin. Eur J Biochem 267:200–206

    Article  PubMed  CAS  Google Scholar 

  • van Delft MF, Wei AH, Mason KD, Vandenberg CJ, Chen L, Czabotar PE, Willis SN, Scott CL, Day CL, Cory S, Adams JM, Roberts AW, Huang DC (2006) The BH3 mimetic ABT-737 targets selective Bcl-2 proteins and efficiently induces apoptosis via Bak/Bax if Mcl-1 is neutralized. Cancer Cell 10:389–399

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Vander Heiden MG, Lunt SY, Dayton TL, Fiske BP, Israelsen WJ, Mattaini KR, Vokes NI, Stephanopoulos G, Cantley LC, Metallo CM, Locasale JW (2011) Metabolic pathway alterations that support cell proliferation. Cold Spring Harb Symp Quant Biol 76:325–334

    Article  PubMed  CAS  Google Scholar 

  • Voet D, Voet JG, Pratt CW (2006) Fundamentals of biochemistry, 2nd edn. Wiley, New York

    Google Scholar 

  • Wallace DC (2012) Mitochondria and cancer. Nat Rev Cancer 12:685–698

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wallace DC, Fan W, Procaccio V (2010) Mitochondrial energetics and therapeutics. Annu Rev Pathol 5:297–348

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wang F, Ogasawara MA, Huang P (2010) Small mitochondria-targeting molecules as anti-cancer agents. Mol Asp Med 31:75–92

    Article  CAS  Google Scholar 

  • Warburg O (1956) On respiratory impairment in cancer cells. Science 124:269–270

    PubMed  CAS  Google Scholar 

  • Warburg O, Dickens F (1930) The metabolism of tumors. Arnold Constable, London

    Google Scholar 

  • Wei AH, Brown M, Guthridge M (2013) The regulation of mitochondrial metabolism by the Bcl-2 family of pro-survival proteins: new therapeutic opportunities for targeting cancer cells. J Hematol Thromb Dis 1:121

    Google Scholar 

  • Weinberg F, Chandel NS (2009) Reactive oxygen species-dependent signaling regulates cancer. Cell Mol Life Sci 66:3663–3673

    Article  PubMed  CAS  Google Scholar 

  • Wong R (2011) Apoptosis in cancer: from pathogenesis to treatment. J Exp Clin Cancer Res 30:87. https://doi.org/10.1186/1756-9966-30-87

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Xu K, Thornalley PJ (2001) Involvement of glutathione metabolism in the cytotoxicity of the phenethyl isothiocyanate and its cysteine conjugate to human leukaemia cells in vitro. Biochem Pharmacol 61:165–177

    Google Scholar 

  • Yamamoto T, Hsu S, Lewis J, Wataha J, Dickinson D, Singh B, Bollag WB, Lockwood P, Ueta E, Osaki T, Schuster G (2003) Green tea polyphenol causes differential oxidative environments in tumor versus normal epithelial cells. J Pharmacol Exp Ther 307:230–236

    Article  PubMed  CAS  Google Scholar 

  • Yang SE, Hsieh MT, Tsai TH, Hsu SL (2002) Down-modulation of Bcl-XL, release of cytochrome c and sequential activation of caspases during honokiol-induced apoptosis in human squamous lung cancer CH27 cells. Biochem Pharmacol 63:1641–1651

    Article  PubMed  CAS  Google Scholar 

  • Yasmin MA, HS EL-A, Mahmoud Marzabani MA, Samia SA (2015) Targeting glycolysis by 3-bromopyruvate improves tamoxifen cytotoxicity of breast cancer cell lines. BMC Cancer 15:838. https://doi.org/10.1186/s12885-015-1850-4

    Article  CAS  Google Scholar 

  • Yong Y, Matthew S, Wittwer J, Pan L, Shen Q, Kinghorn AD, Swanson SM, Carcache De Blanco EJ (2013) Dichamanetin inhibits cancer cell growth by affecting ROS-related signaling components through mitochondrial-mediated apoptosis. Anticancer Res 33:5349–5355

    PubMed  PubMed Central  CAS  Google Scholar 

  • Youle RJ, Strasser A (2008) The Bcl-2 protein family: opposing activities that mediate cell death. Nat Rev Mol Cell Biol 9:47–59

    Article  PubMed  CAS  Google Scholar 

  • Zhang Y, Tang L, Gonzalez V (2003) Selected isothiocyanates rapidly induce growth inhibition of cancer cells. Mol Cancer Ther 2:1045–1052

    PubMed  CAS  Google Scholar 

  • Zhang X, Zhang H, Tighiouart M, Lee JE, Shin HJ, Khuri FR, Yang CS, Chen Z, Shin DM (2008) Synergistic inhibition of head and neck tumor growth by green tea (-)-epigallocatechin-3-gallate and EGFR tyrosine kinase inhibitor. Int J Cancer 123:1005–1114

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zhao Y, Neuzil J, Wu K (2009) Vitamin E analogues as mitochondria-targeting compounds: from the bench to the bedside. Mol Nutr Food Res 53:129–139

    Article  PubMed  CAS  Google Scholar 

  • Zheng SY, Li Y, Jiang D, Zhao J, Ge JF (2012) Anticancer effect and apoptosis induction by quercetin in the human lung cancer cell line A-549. Mol Med Rep 5:822–826

    PubMed  CAS  Google Scholar 

  • Zhivotovsky B, Galluzzi L, Kepp O, Kroemer G (2009) Adenine nucleotide translocase: a component of the phylogenetically conserved cell death machinery. Cell Death Differ 16:1419–1425

    Article  PubMed  CAS  Google Scholar 

  • Zhou Y, Garcia-Prieto C, Carney DA, Xu R, Pelicano H, Kang Y, Yu W, Lou C, Kondo S, Harris JL, Estrov Z, Keating MJ, Jin Z, Huang P (2005) OSW-1: a natural compound with potent anticancer activity and a novel mechanism of action. J Natl Cancer Inst 97:1781–1785

    Article  PubMed  CAS  Google Scholar 

  • Zhu J, Xiong L, Yu B, Wu J (2005) Apoptosis induced by a new member of saponin family is mediated through caspase-8-dependent cleavage of Bcl-2. Mol Pharmacol 68:1831–1838

    PubMed  CAS  Google Scholar 

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Acknowledgment

The authors acknowledge Jaypee Institute of Information Technology, Noida, India, for providing infrastructure to complete this work.

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  1. Department of Biotechnology, Jaypee Institute of Information Technology, Noida, Uttar Pradesh, India

    Shalini Mani, Nancy Taneja, Sweekriti Jain & Manisha Singh

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  1. Shalini Mani
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  4. Manisha Singh
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Correspondence to Shalini Mani .

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  1. Department of Botany, Gandhi Faiz-e-Aam College, Shahjahanpur, Uttar Pradesh, India

    Mohd Sayeed Akhtar

  2. Department of Crop Science,Faculty of Agriculture, Universiti Putra Malaysia, Serdang, Selangor, Malaysia

    Mallappa Kumara Swamy

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Mani, S., Taneja, N., Jain, S., Singh, M. (2018). Anticancerous Plant Compounds Affecting the Power House of Cancerous Cells: A Possible Herbal Mitocan. In: Akhtar, M., Swamy, M. (eds) Anticancer Plants: Mechanisms and Molecular Interactions. Springer, Singapore. https://doi.org/10.1007/978-981-10-8417-1_10

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