Advertisement

Phytochemicals with Anticancer Potential: Methods of Extraction, Basic Structure, and Chemotherapeutic Action

  • Gulrez Nizami
  • R. Z. Sayyed
Chapter

Abstract

Plants have been the integral part of human life and serve as a vital source of many bioactive compounds. The phytochemicals formed during plant’s metabolic processes are potentially useful for a variety of applications in human life. Phytochemicals are generally nonnutritive, naturally occurring chemical compounds which possess medicinal potential or are a source of raw chemicals for the synthesis of medicinally important drugs. Most of the phytochemicals have antioxidant activity, which may protect the human cells against oxidative damage caused by reactive oxygen species, and also minimize the severity of inflammation. Free radical-scavenging phytochemicals, viz., flavonoids, tannins, alkaloids, quinones, amines, vitamins, and other plant metabolites possess anti-inflammatory, anticarcinogenic, antibacterial, and antiviral activities. Flavonoids have been shown to decrease the risk of breast cancer, while the consumption of cruciferous vegetables such as broccoli, cabbage, and cauliflower effectively reduce the chances of prostate, lung, breast, and colon cancers. Sulforaphane found in broccoli is believed to offer some degrees of preventing cancer. The present chapter describes the importance of some plants of the genera Philenoptera (family, Fabaceae), Xanthocercis (family, Fabaceae), and Euphorbia (family, Euphorbiaceae) and crucifer (family, Cruciferae) and their significance in the treatment of cancer and other diseases with respect to their chemical structure and methods of extraction. Moreover, anticancer properties of some important phytochemicals like crocetin, cyanidins, diindolylmethane (DIM) or indole-3-carbinol (I3C), epigallocatechin gallate, fisetin, genistein, gingerol, kaempferol, broccoli, and lycopene have also been discussed.

Keywords

Antioxidants Chemical compounds Drugs Free radicals Phytochemicals 

References

  1. Abdullaev FI, Espinosa-Aguirre JJ (2004) Biomedical properties of saffron and its potential use in cancer therapy and chemoprevention trials. Cancer Detect Prev 28:426–432CrossRefPubMedGoogle Scholar
  2. Acharya A, Das I, Singh S, Saha T (2010) Chemopreventive properties of indole-3-carbinol, diindolylmethane and other constituents of cardamom against carcinogenesis. Recent Pat Food Nutr Agric 2:166–177CrossRefPubMedGoogle Scholar
  3. Amin A, Hamza AA, Bajbouj K, Ashraf SS, Daoud S (2011) Saffron: a potential target for a novel anticancer drug against hepatocellular carcinoma. Hepatology 54:857–867CrossRefPubMedGoogle Scholar
  4. Angelini A, Di Ilio C, Castellani ML, Conti P, Cuccurullo F (2010) Modulation of multidrug resistance p-glycoprotein activity by flavonoids and honokiol in human doxorubicin-resistant sarcoma cells (MES-SA/DX-5): implications for natural sedatives as chemosensitizing agents in cancer therapy. J Biol Regul Homeost Agents 24:197–205PubMedGoogle Scholar
  5. Arai Y, Watanabe S, Kimira M, Shimoi K, Mochizuki R, Kinae N (2000) Dietary intakes of flavonols, flavones and isoflavones by Japanese women and the inverse correlation between quercetin intake and plasma LDL cholesterol concentration. J Nutr 130:2243–2250CrossRefPubMedGoogle Scholar
  6. Aung HH, Wang CZ, Ni M, Fishbein A, Mehendale SR, Xie JT, Shoyama CY, Yuan CS (2007) Crocin from Crocus sativus possesses significant anti-proliferation effects on human colorectal cancer cells. Exp Oncol 29:175–180PubMedPubMedCentralGoogle Scholar
  7. Bakshi H, Sam S, Rozati R, Sultan P, Islam T, Rathore B, Lone Z, Sharma M, Triphati J, Saxena RC (2010) DNA fragmentation and cell cycle arrest: a hallmark of apoptosis induced by crocin from kashmiri saffron in a human pancreatic cancer cell line. Asian Pac J Cancer Prev 11:675–679PubMedGoogle Scholar
  8. Bathaie SZ, Mousavi SZ (2010) New applications and mechanisms of action of saffron and its important ingredients. Crit Rev Food Sci Nutr 50:761–786CrossRefPubMedGoogle Scholar
  9. Bradlow HL, Zeligs MA (2010) Diindolylmethane (DIM) spontaneously forms from indole-3-carbinol (13C) during cell culture experiments. In Vivo 24:387–391PubMedGoogle Scholar
  10. Calderon-Montano JM, Burgos-Moron E, Perez-Guerrero C, Lopez-Lazaro M (2011) A review on the dietary flavonoid kaempferol. Mini-Rev Med Chem 11:298–344CrossRefPubMedGoogle Scholar
  11. Canene-Adams K, Lindshield BL, Wang S, Jeffery EH, Clinton SK, Erdman JW Jr (2007) Combinations of tomato and broccoli enhance antitumor activity in dunning r3327-h prostate adenocarcinomas. Cancer Res 67:836–843CrossRefPubMedGoogle Scholar
  12. Chaimbault P (2014) The modern art of identification of natural substances. In: Jacob C, Kirsch G, Slusarenko AJ, Winyard PG, Burkholz T (eds) Recent advances in redox active plant and microbial products. Springer, Netherlands, pp 31–94Google Scholar
  13. Christophoridou S, Dais P, Tseng LH, Spraul M (2005) Separation and identification of phenolic compounds in olive oil by coupling high performance liquid chromatography with postcolumn solid-phase extraction to nuclear magnetic resonance spectroscopy (LC-SPE-NMR). J Agric Food Chem 53:4667–4679CrossRefPubMedGoogle Scholar
  14. Chryssanthi DG, Dedes PG, Karamanos NK, Cordopatis P, Lamari FN (2011) Crocetin inhibits invasiveness of MDA-MB-231 breast cancer cells via down regulation of matrix metalloproteinases. Planta Med 77:146–151CrossRefPubMedGoogle Scholar
  15. Conforti F, Sosa S, Marrelli M, Menichini F, Statti GA, Uzunov D, Tubaro A, Menichini F, Loggia RD (2008) In vivo anti-inflammatory and in vitro antioxidant activities of Mediterranean dietary plants. J Ethnopharmacol 116:144–151CrossRefPubMedGoogle Scholar
  16. Cui Y, Morgenstern H, Greenland S, Tashkin DP, Mao JT, Cai L, Cozen W, Mack TM, Lu QY, Zhang ZF (2008) Dietary flavonoid intake and lung cancer-a population-based case-control study. Cancer 112:2241–2248CrossRefPubMedPubMedCentralGoogle Scholar
  17. Daffre S, Bulet P, Spisni A, Ehret-sabatier L, Rodrigues EG, Travassos LR (2008) Bioactive natural peptides. Stud Nat Prod Chem 35:597–691CrossRefGoogle Scholar
  18. Dai J, Mumper RJ (2010) Plant phenolics: extraction, analysis and their antioxidant and anticancer properties. Molecules 15:7313–7352CrossRefGoogle Scholar
  19. Das I, Das S, Saha T (2010) Saffron suppresses oxidative stress in DMBA-induced skin carcinoma: a histopathological study. Acta Histochem 112:317–327CrossRefPubMedGoogle Scholar
  20. Dass C (2007) Fundamentals of contemporary mass spectrometry. Wiley, PhiladelphiaCrossRefGoogle Scholar
  21. Emam SS, Abd El-Moaty HI (2009) Glucosinolates, phenolic acids and anthraquinones of Isatis microcarpa Boiss and Pseuderucaria clavate (Boiss & Reut.) family: Cruciferae. J Appl Sci Res 5:2315–2322Google Scholar
  22. Gacche RN, Shegokar HD, Gond DS, Yang Z, Jadhav AD (2011) Evaluation of selected flavonoids as antiangiogenic, anticancer, and radical scavenging agents: an experimental and in silico analysis. Cell Biochem Biophys 61:651–663CrossRefPubMedGoogle Scholar
  23. Geraets L, Haegens A, Brauers K, Haydock JA, Vernooy JH, Wouters EF, Bast A, Hageman GJ (2009) Inhibition of LPS-induced pulmonary inflammation by specific flavonoids. Biochem Biophys Res Commun 382:598–603CrossRefPubMedGoogle Scholar
  24. Giovannucci E, Ascherio A, Rimm EB, Stampfer MJ, Colditz GA, Willett WC (1995) Intake of carotenoids and retinol in relation to risk of prostate cancer. J Natl Cancer Inst 87:1767–1776CrossRefPubMedGoogle Scholar
  25. Greer JB, Modugno F, Allen GO, Ness RB (2005) Androgenic progestins in oral contraceptives and the risk of epithelial ovarian cancer. Obstet Gynecol 105:731–740CrossRefPubMedGoogle Scholar
  26. Harborne JB, Williams CA (1992) Advances in flavonoid research since 1992. Phytochemistry 55:481–504CrossRefGoogle Scholar
  27. Howitz KT, Bitterman KJ, Cohen HY, Lamming DW, Lavu S, Wood JG, Zipkin RE, Chung P, Kisielewski A, Zhang LL, Scherer B, Sinclair DA (2003) Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature 425:191–196CrossRefPubMedGoogle Scholar
  28. Jeong CH, Bode AM, Pugliese A, Cho YY, Kim HG, Shim JH, Jeon YJ, Li H, Jiang H, Dong Z (2009) [6]-Gingerol suppresses colon cancer growth by targeting leukotriene A4 hydrolase. Cancer Res 69:5584–5591CrossRefPubMedGoogle Scholar
  29. Jiang Z, Kempinski C, Chappell J (2016) Extraction and analysis of terpenes/terpenoids. Curr Protoc Plant Biol 1:345–358CrossRefPubMedPubMedCentralGoogle Scholar
  30. Kahkonen MP, Hopia AI, Vuorela HJ, Rauha JP, Pihlaja K, Kujala TS, Heinonen M (1999) Antioxidant activity of plant extracts containing phenolic compounds. J Agric Food Chem 47:3954–3962CrossRefPubMedGoogle Scholar
  31. Kaskiw MJ, Tassotto ML, Mok M, Tokar SL, Pycko R, Thng J, Jiang ZH (2009) Structural analogues of diosgenyl saponins: synthesis and anticancer activity. Bioorg Med Chem 17:7670–7679CrossRefPubMedGoogle Scholar
  32. Khan N, Afaq F, Khusro FH, Adhami VM, Suh Y, Mukhtar H (2012) Dual inhibition of phosphatidylinositol 3-kinase/Akt and mammalian target of rapamycin signaling in human non small cell lung cancer cells by a dietary flavonoid fisetin. Int J Cancer 130:1695–1705CrossRefPubMedGoogle Scholar
  33. Kim YS, Milner JA (2005) Targets for indole-3-carbinol in cancer prevention. J Nutr Biochem 16:65–73CrossRefPubMedGoogle Scholar
  34. Kim JM, Kim JS, Yoo H, Choung MG, Sung MK (2008) Effects of black soybean [Glycine max (L.) Merr.] seed coats and its anthocyanidins on colonic inflammation and cell proliferation in vitro and in vivo. J Agric Food Chem 56:8427–8433CrossRefPubMedGoogle Scholar
  35. Kim JE, Kwon JY, Seo SK, Son JE, Jung SK, Min SY, Hwang MK, Heo YS, Lee KW, Lee HJ (2010) Cyanidin suppresses ultraviolet B-induced COX-2 expression in epidermal cells by targeting MKK4, MEK1, and Raf-1. Biochem Pharmacol 79:1473–1482CrossRefPubMedGoogle Scholar
  36. Kinghorn A, Farnsworth N, Soejarto D, Cordell G, Swanson S, Pezzuto J, Wani M, Wall M, Oberlies N, Kroll D, Kramer R, Rose W, Vite G, Fairchild C, Peterson R, Wild R (2003) Novel strategies for the discovery of plant derived anticancer agents. Pharm Biol 41:53–67CrossRefGoogle Scholar
  37. Lee HS, Seo EY, Kang NE, Kim WK (2008) [6]-Gingerol inhibits metastasis of MDA MB-231 human breast cancer cells. J Nutr Biochem 19:313–319CrossRefPubMedGoogle Scholar
  38. Liao YC, Shih YW, Chao CH, Lee XY, Chiang TA (2009) Involvement of the ERK signaling pathway in fisetin reduces invasion and migration in the human lung cancer cell line A549. J Agric Food Chem 57:8933–8941CrossRefPubMedGoogle Scholar
  39. Lim DY, Park JH (2009) Induction of p53 contributes to apoptosis of HCT-116 human colon cancer cells induced by the dietary compound fisetin. Am J Physiol Gastrointest Liver Physiol 296:G1060–G1068CrossRefPubMedGoogle Scholar
  40. Lim TG, Kwon JY, Kim J, Song NR, Lee KM, Heo YS, Lee HJ, Lee KW (2011) Cyanidin-3-glucoside suppresses B[a]PDE-induced cyclooxygenase-2 expression by directly inhibiting Fyn kinase activity. Biochem Pharmacol 82:167–174CrossRefPubMedGoogle Scholar
  41. Liu RH (2004) Potential synergy of phytochemicals in cancer prevention: mechanism of action. J Nutr 134:S3479–S3485CrossRefGoogle Scholar
  42. Londono JL, de Lima VR, Lara O, Gil A, Pasa TBC, Arango GJ, Pineda JRR (2010) Clean recovery of antioxidant flavonoids from citrus peel: optimizing an aqueous ultrasound-assisted extraction method. Food Chem 119:81–87CrossRefGoogle Scholar
  43. Lopez-Lazaro M, Willmore E, Austin CA (2007) Cells lacking DNA topoisomerase II beta are resistant to genistein. J Nat Prod 70:763–767CrossRefPubMedGoogle Scholar
  44. Maher P, Dargusch R, Ehren JL, Okada S, Sharma K, Schubert D (2011) Fisetin lowers methylglyoxal dependent protein glycation and limits the complications of diabetes. PLoS One 6:e21226.  https://doi.org/10.1371/journal.pone.0021226 CrossRefPubMedPubMedCentralGoogle Scholar
  45. Monte J, Abreu AC, Borges A, Simoes LC, Simoes M (2014) Antimicrobial activity of selected phytochemicals against Escherichia coli and Staphylococcus aureus and their biofilms. Pathogens 3:473–498CrossRefPubMedPubMedCentralGoogle Scholar
  46. Nahum A, Hirsch K, Danilenko M, Watts CK, Prall OW, Levy J, Sharoni Y (2001) Lycopene inhibition of cell cycle progression in breast and endometrial cancer cells is associated with reduction in cyclin D levels and retention of p27(Kip1) in the cyclin E-cdk2 complexes. Oncogene 20:3428–3436CrossRefPubMedGoogle Scholar
  47. Nam KN, Park YM, Jung HJ, Lee JY, Min BD, Park SU, Jung WS, Cho KH, Park JH, Kang I, Hong JW, Lee EH (2010) Anti-inflammatory effects of crocin and crocetin in rat brain microglial cells. Eur J Pharmacol 648:110–116CrossRefPubMedGoogle Scholar
  48. Narod SA, Risch H, Moslehi R, Dorum A, Neuhausen S, Olsson H, Provencher D, Radice P, Evans G, Bishop S, Brunet JS, Ponder BA (1998) Oral contraceptives and the risk of hereditary ovarian cancer. New Eng J Med 339:424–428CrossRefPubMedGoogle Scholar
  49. Ning G, Tianhua L, Xin Y, He P (2009) Constituents in Desmodium blandum and their antitumor activity. Chin Trad Herb Drug 40:852–856Google Scholar
  50. Nothlings U, Murphy SP, Wilkens LR, Henderson BE, Kolonel LN (2007) Flavonols and pancreatic cancer risk: the multiethnic cohort study. Am J Epidemiol 166:924–931CrossRefPubMedGoogle Scholar
  51. Okwu DE (2005) Phytochemicals, vitamin and mineral contents of two Nigeria medicinal plants. Int J Mol Med Adv Sci 1:375–381Google Scholar
  52. Oyagbemi AA, Saba AB, Azeez OI (2010) Molecular targets of [6]-gingerol: its potential roles in cancer chemoprevention. Biofactors 36:169–178CrossRefPubMedGoogle Scholar
  53. Park YJ, Wen J, Bang S, Park SW, Song SY (2006) [6]-Gingerol induces cell cycle arrest and cell death of mutant p53-expressing pancreatic cancer cells. Yonsei Med J 47:688–697CrossRefPubMedPubMedCentralGoogle Scholar
  54. Patil PS, Shettigar R (2010) An advancement of analytical techniques in herbal research. J Adv Sci Res 1:8–14Google Scholar
  55. Peter M (2013) Ethnobotanical study of some selected medicinal plants used by traditional healers in Limpopo province (South Africa). Am J Res Commun 1:8–23Google Scholar
  56. Rahman AU, Choudhary MI (2001) Bioactive natural products as potential source of new pharmacophores. A theory of memory. Pure Appl Chem 73:555–560CrossRefGoogle Scholar
  57. Raynal NJ, Momparler L, Charbonneau M, Momparler RL (2008) Antileukemic activity of genistein, a major isoflavone present in soy products. J Nat Prod 71:3–7CrossRefPubMedGoogle Scholar
  58. Rhazi N, Hannache H, Oumam M, Sesbou A, Charrier B, Pizzi A, Charrier-El Bouhtoury F (2015) Green extraction process of tannins obtained from Moroccan Acacia mollissima barks by microwave: modeling and optimization of the process using the response surface methodology RSM. Arab J Chem (Online).  https://doi.org/10.1016/j.arabjc.2015.04.032
  59. Rhode J, Fogoros S, Zick S, Wahl H, Griffith KA, Huang J, Liu JR (2007) Ginger inhibits cell growth and modulates angiogenic factors in ovarian cancer cells. BMC Compl Altern Med 7:44Google Scholar
  60. Sala A, Recio MD, Giner RM, Manez S, Tournier H, Schinella G, Rios JL (2002) Antiinflammatory and antioxidant properties of Helichrysum italicum. J Pharm Pharmacol 54:365–371CrossRefPubMedGoogle Scholar
  61. Samarghandian S, Tavakkol Afshari J, Davoodi S (2010) Suppression of pulmonary tumor promotion and induction of apoptosis by Crocus sativus L. extraction. Appl Biochem Biotechnol 164:238–247CrossRefPubMedGoogle Scholar
  62. Samarghandian S, Boskabady MH, Davoodi S (2011) Use of in vitro assays to assess the potential antiproliferative and cytotoxic effects of saffron (Crocus sativus L.) in human lung cancer cell line. Pharmacogn Mag 6:309–314CrossRefGoogle Scholar
  63. Sanchez Y, Amran D, de Blas E, Aller P (2009) Regulation of genistein-induced differentiation in human acute myeloid leukaemia cells (HL60, NB4) protein kinase modulation and reactive oxygen species generation. Biochem Pharmacol 77:384–396CrossRefPubMedGoogle Scholar
  64. Shami AM (2015) Isolation and identification of anthraquinones extracted from Morinda citrifolia L. (Rubiaceae). Ann Chromatogr Sep Tech 1:1012Google Scholar
  65. Shapiro TA, Fahey JW, Wade KL, Stephenson KK, Talalay P (2001) Chemoprotective glucosinolates and isothiocyanates of broccoli sprouts: metabolism and excretion in humans. Cancer Epidemiol Biomark Prev 10:501–508Google Scholar
  66. Shirwaikar A, Rajendran K, Punitha IS (2006) In vitro anti-oxidant studies on the benzyl tetra isoquinoline alkaloid berberine. Biol Pharm Bull 29:1906–1910CrossRefPubMedGoogle Scholar
  67. Smith RD, Wright BW, Yonker CR (1988) Supercritical fluid chromatography: current status and prognosis. Anal Chem 60:A1323–A1336CrossRefGoogle Scholar
  68. Stray F, Storchova H (1991) The natural guide to medicinal herbs and plants, 2nd edn. Dorset House Publishing, New York, p 223Google Scholar
  69. Wang W, Bringe NA, Berhow MA, Gonzalez de Mejia E (2008) Beta-conglycinins among sources of bioactives in hydrolysates of different soybean varieties that inhibit leukemia cells in vitro. J Agric Food Chem 56:4012–4020CrossRefPubMedGoogle Scholar
  70. Watson AA, Fleet GWJ, Asano N, Molyneux RJ, Nash RJ (2001) Polyhydroxylated alkaloids-natural occurrence and therapeutic applications. Phytochemistry 56:265–295CrossRefPubMedGoogle Scholar
  71. Williams RJ, Spencer JP, Rice-Evans C (2004) Flavonoids: antioxidants or signalling molecules. Free Radic Biol Med 36:838–849CrossRefPubMedGoogle Scholar
  72. Wong TS, Roccatano D, Zacharias M, Schwaneberg U (2006) A statistical analysis of random mutagenesis methods used for directed protein evolution. J Mol Biol 355:858–871CrossRefPubMedGoogle Scholar
  73. Wood JG, Rogina B, Lavu S, Howitz K, Helfand SL, Tatar M, Sinclair D (2004) Sirtuin activators mimic caloric restriction and delay ageing in metazoans. Nature 430:686–689CrossRefPubMedGoogle Scholar
  74. Wrobleski A, Sahasrabudhe K, Aube J (2004) Asymmetric total synthesis of dendrobatid alkaloids: preparation of indolizidine 251f and its 3-desmethyl analogue using an intramolecular schmidt reaction. J Am Chem Soc 28:426–432Google Scholar
  75. Xie P, Chen S, Liang YZ, Wang X, Tian R, Upton R (2006) Chromatographic fingerprint analysis-a rational approach for quality assessment of traditional Chinese herbal medicine. J Chromatogr 1112:171–180CrossRefGoogle Scholar
  76. Xu M, Bower KA, Wang S, Frank JA, Chen G, Ding M, Wang S, Shi X, Ke Z, Luo J (2011) Cyanidin-3-glucoside inhibits ethanol-induced invasion of breast cancer cells overexpressing ErbB2. Mol Cancer 9:285.  https://doi.org/10.1186/1476-4598-9-285 CrossRefGoogle Scholar
  77. Yamasaki M, Fujita S, Ishiyama E, Mukai A, Madhyastha H, Sakakibara Y, Suiko M, Hatakeyama K, Nemoto T, Morishita K, Kataoka H, Tsubouchi H, Nishiyama K (2007) Soy-derived isoflavones inhibit the growth of adult T-cell leukemia cells in vitro and in vivo. Cancer Sci 98:1740–1746CrossRefPubMedGoogle Scholar
  78. Yan LL, Zhang YJ, Gao WY, Man SL, Wang Y (2009) In vitro and in vivo anticancer activity of steroid saponins of Paris polyphylla var. yunnanensis. Exp Oncol 31:27–32PubMedGoogle Scholar
  79. Zikri NN, Ried KM, Wang LS, Lechner J, Schwartz SJ, Stoner GD (2009) Black raspberry components inhibit proliferation, induce apoptosis, and modulate gene expression in rat esophageal epithelial cells. Nutr Cancer 61:816–826CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  • Gulrez Nizami
    • 1
  • R. Z. Sayyed
    • 2
  1. 1.Department of ChemistryMohammad Ali Jauhar UniversityRampurIndia
  2. 2.Department of MicrobiologyPSGVP Mandal’s Arts, Science and Commerce CollegeShahadaIndia

Personalised recommendations