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Antitumour activities of sanguinarine and related alkaloids

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Abstract

Sanguinarine is a best-known member of a relatively small group of quaternary benzo[c]phenanthridine alkaloids (QBAs). QBAs are widely distributed in the family Papaveraceae and, to a limited extent, in some species of the families Fumariaceae and Rutaceae. From a medical perspective, QBAs have many important properties. In addition to antitumour activity, they display antimicrobial, antifungal and anti-inflammatory effects. They may interact with many targets, such as DNA and microtubules, and they modify the activities of a wide variety of enzymes. This review summarises the current state of knowledge about the properties of QBAs that are important for their potential use in anticancer therapy.

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Abbreviations

Bcl2:

B-cell lymphoma 2 protein

DHSA:

Dihydrosanguinarine

CHE:

Chelerythrine

CHL:

Chelilutine

CHLD:

Chelidonine

CHR:

Chelirubine

MA:

Macarpine

MAPK:

Mitogen-activated protein kinase

MT:

Microtubule

NAC:

N-acetylcysteine

NK109:

7-Hydroxy-8-methoxy-5-methyl-2,3methylenedioxybenzo[c]phenanthridinium hydrogen sulfate

NK314:

4-Hydroxy-5-methoxy-2,3-dihydro-1H-[1,3]benzodioxolo[5,6-c]pyrrolo[1,2-f]-phenanthridinium chloride

QBAs:

Quaternary benzo[c]phenanthridine alkaloids

ROS:

Reactive oxygen species

SA:

Sanguinarine

SL:

Sanguilutine

SR:

Sanguirubine

TRAIL:

Tumour necrosis factor-related apoptosis-inducing ligand

CDK:

Cyclin-dependent kinase

DHF-DA:

Dihydrofluorescein diacetate

DR4 5:

Death receptor 4 and 5

γH2AX:

Phosphorylated histone H2AX

IAP:

Inhibitor of apoptosis

MMP-2 MMP-9:

Matrix metalloproteinase-2 and 9

RIP:

Receptor-interacting protein

VEGF:

Vascular endothelial growth factor

References

  • Aburai N, Yoshida M, Ohnishi M et al (2010) Sanguinarine as a potent and specific inhibitor of protein phosphatase 2C in vitro and induces apoptosis via phosphorylation of p38 in HL60 cells. Biosci Biotechnol Biochem 74:548–552

    CAS  PubMed  Google Scholar 

  • Adhami VM, Aziz MH, Mukhtar H et al (2003) Activation of prodeath Bcl-2 family proteins and mitochondrial apoptosis pathway by sanguinarine in immortalized human HaCaT keratinocytes. Clin Cancer Res 9:3176–3182

    CAS  PubMed  Google Scholar 

  • Adhami VM, Aziz MH, Reagan-Shaw SR et al (2004) Sanguinarine causes cell cycle blockade and apoptosis of human prostate carcinoma cells via modulation of cyclin kinase inhibitor-cyclin-cyclin-dependent kinase machinery. Mol Cancer Ther 3:933–940

    CAS  PubMed  Google Scholar 

  • Adhikari A, Hossain M, Maiti M et al (2008) Energetics of the binding of phototoxic and cytotoxic plant alkaloid sanguinarine to DNA: isothermal titration calorimetric studies. J Mol Struct 889:54–63

    CAS  Google Scholar 

  • Ahmad N, Gupta S, Husain MM et al (2000) Differential anti-proliferative and apoptotic response of sanguinarine for cancer cells versus normal cells. Clin Cancer Res 6:1524–1528

    CAS  PubMed  Google Scholar 

  • Ahsan H, Reagan-Shaw S, Breur J et al (2007a) Sanguinarine induces apoptosis of human pancreatic carcinoma AsPC-1 and BxPC-3 cells via modulations in Bcl-2 family proteins. Cancer Lett 249:198–208

    CAS  PubMed  Google Scholar 

  • Ahsan H, Reagan-Shaw S, Eggert DM et al (2007b) Protective effect of sanguinarine on ultraviolet B-mediated damages in SKH-1 hairless mouse skin: implications for prevention of skin cancer. Photochem Photobiol 83:986–993

    CAS  PubMed  Google Scholar 

  • Alcantara J, Bird DA, Franceschi VR et al (2005) Sanguinarine biosynthesis is associated with the endoplasmic reticulum in cultured opium poppy cells after elicitor treatment. Plant Physiol 138:173–183

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ansari KM, Das M (2010) Skin tumor promotion by argemone oil/alkaloid in mice: evidence for enhanced cell proliferation, ornithine decarboxylase, cyclooxygenase-2 and activation of MAPK/NF-kappaB pathway. Food Chem Toxicol 48:132–138

    CAS  PubMed  Google Scholar 

  • Babu ChK, Khanna SK, Das M (2006) Safety evaluation studies on argemone oil through dietary exposure for 90 days in rats. Food Chem Toxicol 44:1151–1157

    CAS  PubMed  Google Scholar 

  • Bai LP, Zhao ZZ, Cai ZW et al (2006) DNA-binding affinities and sequence selectivity of quaternary benzophenanthridine alkaloids sanguinarine, chelerythrine, and nitidine. Bioorg Med Chem 14:5439–5445

    CAS  PubMed  Google Scholar 

  • Bai LP, Cai ZW, Zhao ZZ et al (2008) Site-specific binding of chelerythrine and sanguinarine to single pyrimidine bulges in hairpin DNA. Anal Bioanal Chem 392:709–716

    CAS  PubMed  Google Scholar 

  • Barreto MC, Pinto RE, Arrabaca JD et al (2003) Inhibition of mouse liver respiration by Chelidonium majus isoquinoline alkaloids. Toxicol Lett 146:37–47

    CAS  PubMed  Google Scholar 

  • Basini G, Santini SE, Bussolati S et al (2007) The plant alkaloid sanguinarine is a potential inhibitor of follicular angiogenesis. J Reprod Dev 53:573–579

    CAS  PubMed  Google Scholar 

  • Bessi I, Bazzicalupi C, Richter C et al (2012) Spectroscopic, molecular modeling, and NMR-spectroscopic investigation of the binding mode of the natural alkaloids berberine and sanguinarine to human telomeric G-quadruplex DNA. ACS Chem Biol 7:1109–1119

    CAS  PubMed  Google Scholar 

  • Bhadra K, Kumar GS (2011) Interaction of berberine, palmatine, coralyne, and sanguinarine to quadruplex DNA: a comparative spectroscopic and calorimetric study. Biochim Biophys Acta 1810:485–496

    CAS  PubMed  Google Scholar 

  • Booth NL, Sayers TJ, Brooks AD et al (2008) A cell-based high-throughput screen to identify synergistic TRAIL sensitizers. Cancer Immunol Immunother 58:1229–1244

    PubMed Central  PubMed  Google Scholar 

  • Chan SL, Lee MC, Tan KO et al (2003) Identification of chelerythrine as an inhibitor of BclXL function. J Biol Chem 278:20453–20456

    CAS  PubMed  Google Scholar 

  • Chang MC, Chan CP, Wang YJ et al (2007) Induction of necrosis and apoptosis to KB cancer cells by sanguinarine is associated with reactive oxygen species production and mitochondrial membrane depolarization. Toxicol Appl Pharmacol 218:143–151

    CAS  PubMed  Google Scholar 

  • Choi WY, Kim GY, Lee WH et al (2008) Sanguinarine, a benzophenanthridine alkaloid, induces apoptosis in MDA-MB-231 human breast carcinoma cells through a reactive oxygen species-mediated mitochondrial pathway. Chemotherapy 54:279–287

    CAS  PubMed  Google Scholar 

  • Choi WY, Jin CY, Han MH et al (2009a) Sanguinarine sensitizes human gastric adenocarcinoma AGS cells to TRAIL-mediated apoptosis via down-regulation of AKT and activation of caspase-3. Anticancer Res 29:4457–4465

    CAS  PubMed  Google Scholar 

  • Choi YH, Choi WY, Hong SH et al (2009b) Anti-invasive activity of sanguinarine through modulation of tight junctions and matrix metalloproteinase activities in MDA-MB-231 human breast carcinoma cells. Chem Biol Interact 179:185–191

    CAS  PubMed  Google Scholar 

  • Choi J, He N, Sung MK et al (2011) Sanguinarine is an allosteric activator of AMP-activated protein kinase. Biochem Biophys Res Commun 413:259–263

    CAS  PubMed  Google Scholar 

  • Choy CS, Cheah KP, Chiou HY et al (2008) Induction of hepatotoxicity by sanguinarine is associated with oxidation of protein thiols and disturbance of mitochondrial respiration. J Appl Toxicol 28:945–956

    CAS  PubMed  Google Scholar 

  • Das M, Ansari KM, Dhawan A et al (2005) Correlation of DNA damage in epidemic dropsy patients to carcinogenic potential of argemone oil and isolated sanguinarine alkaloid in mice. Int J Cancer 117:709–717

    CAS  PubMed  Google Scholar 

  • De Stefano I, Raspaglio G, Zannoni GF et al (2009) Antiproliferative and antiangiogenic effects of the benzophenanthridine alkaloid sanguinarine in melanoma. Biochem Pharmacol 78:1374–1381

    PubMed  Google Scholar 

  • Debiton E, Madelmont JC, Legault J et al (2003) Sanguinarine-induced apoptosis is associated with an early and severe cellular glutathione depletion. Cancer Chemother Pharmacol 51:474–482

    CAS  PubMed  Google Scholar 

  • Degterev A, Hitomi J, Germscheid M et al (2008) Identification of RIP1 kinase as a specific cellular target of necrostatins. Nat Chem Biol 4:313–321

    CAS  PubMed  Google Scholar 

  • Deroussent A, Ré M, Hoellinger H et al (2010) Metabolism of sanguinarine in human and in rat: characterization of oxidative metabolites produced by human CYP1A1 and CYP1A2 and rat liver microsomes using liquid chromatography-tandem mass spectrometry. J Pharm Biomed Anal 52:391–397

    CAS  PubMed  Google Scholar 

  • Ding Z, Tang SC, Weerasinghe P et al (2002) The alkaloid sanguinarine is effective against multidrug resistance in human cervical cells via bimodal cell death. Biochem Pharmacol 63:1415–1421

    CAS  PubMed  Google Scholar 

  • Dostál J, Slavík J (2002) Some aspects of the chemistry of quaternary benzo[c]phenanthridine alkaloids. Stud Nat Prod Chem 27:155–184

    Google Scholar 

  • Dvořák Z, Kubán V, Klejdus B et al (2006) Quaternary benzo[c]phenanthridines sanguinarine and chelerythrine: a review of investigations from chemical and biological studies. Heterocycles 68:2403–2422

    Google Scholar 

  • Eun JP, Koh GY (2004) Suppression of angiogenesis by the plant alkaloid sanguinarine. Biochem Biophys Res Commun 317:618–624

    CAS  PubMed  Google Scholar 

  • Fukuda M, Inomata M, Nishio K et al (1996) A topoisomerase II inhibitor, NK109, induces DNA single- and double-strand breaks and apoptosis. Jpn J Cancer Res 87:1086–1091

    CAS  PubMed  Google Scholar 

  • Funakoshi T, Aki T, Nakayama H et al (2011) Reactive oxygen species-independent rapid initiation of mitochondrial apoptotic pathway by chelerythrine. Toxicol In Vitro 25:1581–1587

    CAS  PubMed  Google Scholar 

  • Guo L, Liu XJ, Nishikawa K et al (2007) Inhibition of topoisomerase II alpha and G2 cell cycle arrest by NK314, a novel benzo[c]phenanthridine currently in clinical trials. Mol Cancer Ther 6:1501–1508

    CAS  PubMed  Google Scholar 

  • Guo L, Liu X, Nishikawa K et al (2011) DNA-dependent protein kinase and ataxia telangiectasia mutated (ATM) promote cell survival in response to NK314, a topoisomerase IIα inhibitor. Mol Pharmacol 80:321–327

    CAS  PubMed  Google Scholar 

  • Hammerová J, Uldrijan S, Táborská E et al (2011) Benzo[c]phenanthridine alkaloids exhibit strong anti-proliferative activity in malignant melanoma cells regardless of their p53 status. J Dermatol Sci 62:22–35

    PubMed  Google Scholar 

  • Hammerová J, Uldrijan S, Táborská E et al (2012) Necroptosis modulated by autophagy is a predominant form of melanoma cell death induced by sanguilutine. Biol Chem 393:647–658

    PubMed  Google Scholar 

  • Han MH, Yoo YH, Choi YH (2008) Sanguinarine-induced apoptosis in human leukemia U937 cells via bcl-2 downregulation and caspase-3 activation. Chemotherapy 54:157–165

    CAS  PubMed  Google Scholar 

  • Herbert JM, Augereau JM, Gleye J et al (1990) Chelerythrine is a potent and specific inhibitor of protein kinase C. Biochem Biophys Res Commun 172:993–999

    CAS  PubMed  Google Scholar 

  • Hisatomi T, Sueoka-Aragane N, Sato A et al (2011) NK314 potentiates antitumor activity with adult T-cell leukemia-lymphoma cells by inhibition of dual targets on topoisomerase II alpha and DNA-dependent protein kinase. Blood 117:3575–3784

    CAS  PubMed  Google Scholar 

  • Holy J, Laminy G, Perkins E (2006) Disruption of nucleocytoplasmic trafficking of cyclin D1 and topoisomerase II by sanguinarine. BMC Cell Biol 7:13

    PubMed Central  PubMed  Google Scholar 

  • Hossain M, Kumar GS (2009) DNA binding of benzophenanthridine compounds sanguinarine versus ethidium: comparative binding and thermodynamic profile of intercalation. J Chem Thermodyn 41:764–774

    CAS  Google Scholar 

  • Hossain M, Khan A, Kumar Y (2012) Study on the thermodynamics of the binding of iminium and alkanolamine forms of the anticancer agent sanguinarine to human serum albumin. J Chem Thermodyn 47:90–99

    CAS  Google Scholar 

  • Hussain AR, Al-Jomah NA, Siraj AK et al (2007) Sanguinarine-dependent induction of apoptosis in primary effusion lymphoma cells. Cancer Res 67:3888–3897

    CAS  PubMed  Google Scholar 

  • Jang BC, Park JG, Song DK et al (2009) Sanguinarine induces apoptosis in A549 human lung cancer cells primarily via cellular glutathione depletion. Toxicol In Vitro 23:281–287

    CAS  PubMed  Google Scholar 

  • Janovská M, Kubala M, Šimánek V et al (2010) Interaction of sanguinarine and its dihydroderivative with the Na+/K+-ATPase. complex view on the old problem. Toxicol Lett 196:56–59

    PubMed  Google Scholar 

  • Ji XH, Sun HX, Zhou HX et al (2012) The interaction of telomeric DNA and C-myc22 G-quadruplex with 11 natural alkaloids. Nucleic Acid Ther 22:127–136

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kaminskyy VO, Lootsik MD, Stoika RS (2006) Correlation of the cytotoxic activity of four different alkaloids from Chelidonium majus (greater celandine), with their DNA intercalatin properties and ability to induce breaks in the DNA of NK/Ly murine lymphoma cells. Eur J Biol 1:2–15

    CAS  Google Scholar 

  • Kaminskyy V, Kulachkovskyy O, Stoika R (2008a) A decisive role of mitochondria in defining rate and intensity of apoptosis induction by different alkaloids. Toxicol Lett 177:168–181

    CAS  PubMed  Google Scholar 

  • Kaminskyy V, Lin KW, Filyak Y et al (2008b) Differential effect of sanguinarine, chelerythrine and chelidonine on DNA damage and cell viability in primary mouse spleen cells and mouse leukemic cells. Cell Biol Int 32:271–277

    CAS  PubMed  Google Scholar 

  • Karp JM, Rodrigo KA, Pei P et al (2005) Sanguinarine activates polycyclic aromatic hydrocarbon associated metabolic pathways in human oral keratinocytes and tissues. Toxicol Lett 158:50–60

    CAS  PubMed  Google Scholar 

  • Kemény-Beke A, Aradi J, Damjanovich J et al (2006) Apoptotic response of uveal melanoma cells upon treatment with chelidonine, sanguinarine and chelerythrine. Cancer Lett 237:67–75

    PubMed  Google Scholar 

  • Kim S, Lee TJ, Leem J et al (2008) Sanguinarine-induced apoptosis: generation of ROS, down-regulation of Bcl-2, c-FLIP, and synergy with TRAIL. J Cell Biochem 104:895–907

    CAS  PubMed  Google Scholar 

  • Kosina P, Walterová D, Ulrichová J et al (2004) Sanguinarine and chelerythrine: assessment of safety on pigs in ninety days feeding experiment. Food Chem Toxicol 42:85–91

    CAS  PubMed  Google Scholar 

  • Kosina P, Vacek J, Papoušková B et al (2011) Identification of benzo[c]phenanthridine metabolites in human hepatocytes by liquid chromatography with electrospray ion-trap and quadrupole time-of-flight mass spektrometry. J Chromatogr B 879:1077–1085

    CAS  Google Scholar 

  • Kovář J, Stejskal J, Paulová H et al (1986) Reduction of quaternary benzophenanthridine alkaloids by NADH and NADPH. Collect Czech Chem Commun 51:2626–2634

    Google Scholar 

  • Lee SS, Kai M, Lee MK (2001) Inhibitory effects of sanguinarine on monoamine oxidase activity in mouse brain. Phytother Res 15:167–169

    CAS  PubMed  Google Scholar 

  • Lee B, Park SS, Kim SK et al (2008) Sanguinarine-induced G1-phase arrest of the cell cycle results from increased p27KIP1 expression mediated via activation of the Ras/ERK signaling pathway in vascular smooth muscle cells. Arch Biochem Biophys 471:224–231

    CAS  PubMed  Google Scholar 

  • Li JF, Li BH, Wu YB et al (2012) Luminescence and binding properties of two isoquinoline alkaloids chelerythrine and sanguinarine with ctDNA. Spectrochim Acta Pt A Mol Biomol Spectrosc 95:80–85

    CAS  Google Scholar 

  • Lopus M, Panda D (2006) The benzophenanthridine alkaloid sanguinarine perturbs microtubule assembly dynamics through tubulin binding. FEBS J 273:2139–2150

    CAS  PubMed  Google Scholar 

  • Maiti M, Kumar GS (2007) Molecular aspects on the interaction of protoberberine, benzophenanthridine, and aristolochia group of alkaloids with nucleic acid structures and biological perspectives. Med Res Rev 27:649–695

    CAS  PubMed  Google Scholar 

  • Maiti M, Nandi R, Chaudhuri K (1982) Sanguinarine-a monofunctional intercalating alkaloid. FEBS Lett 142:280–284

    CAS  PubMed  Google Scholar 

  • Maiti M, Nandi R, Chaudhuri K (1984) Interaction of sanguinarine with natural and synthetic deoxyribonucleic acids. Indian J Biochem Biol 21:158–165

    CAS  Google Scholar 

  • Malíková J, Zdařilová A, Hlobilková A et al (2006) The effect of chelerythrine on cell growth, apoptosis, and cell cycle in human normal and cancer cells in comparison with sanguinarine. Cell Biol Toxicol 22:439–453

    PubMed  Google Scholar 

  • Matkar SS, Wrischnik LA, Hellmann-Blumberg U (2008a) Sanguinarine causes DNA damage and p53-independent cell death in human colon cancer cell lines. Chem Biol Interact 172:63–71

    CAS  PubMed  Google Scholar 

  • Matkar SS, Wrischnik LA, Hellmann-Blumberg U (2008b) Production of hydrogen peroxide and redox cycling can explain how sanguinarine and chelerythrine induce rapid apoptosis. Arch Biochem Biophys 477:43–52

    CAS  PubMed  Google Scholar 

  • Morohashi K, Yoshino A, Yoshimori A et al (2005) Identification of a drug target motif: an anti-tumor drug NK109 interacts with a PNxxxxP. Biochem Pharmacol 70:37–46

    CAS  PubMed  Google Scholar 

  • Nakanishi T, Suzuki M (1999) Synthesis and cytotoxic activities of a new benzo[c]phenanthridine alkaloid, 7-hydroxynitidine, and some 9-oxygenated benzo[c]phenanthridine derivatives. Org Lett 1:985–988

    CAS  PubMed  Google Scholar 

  • Nakanishi T, Suzuki M, Saimoto A et al (1999) Structural considerations of NK109, an antitumor benzo[c]phenanthridine alkaloid. J Nat Prod 62:864–867

    CAS  PubMed  Google Scholar 

  • Nakanishi T, Masuda A, Suwa M et al (2000) Synthesis of derivatives of NK109, 7-OH benzo[c]phenanthridine alkaloid, and evaluation of their cytotoxicities and reduction-resistant properties. Bioorg Med Chem Lett 10:2321–2323

    CAS  PubMed  Google Scholar 

  • Newman DJ, Cragg GM (2012) Natural products as sources of new drugs over the 30 years from 1981 to 2010. J Nat Prod 75:311–335

    CAS  PubMed Central  PubMed  Google Scholar 

  • Paulová H, Slavík J (1993) Interaction of sanguinarine with human serum-albumin. Pharmazie 48:555–556

    PubMed  Google Scholar 

  • Pěnčíková K, Kollár P, Müller-Závalová V et al (2012) Investigation of sanguinarine and chelerythrine effects on LPS-induced inflammatory gene expression in THP-1 cell line. Phytomedicine 19:890–895

    PubMed  Google Scholar 

  • Philchenkov A, Kaminskyy V, Zavelevich M et al (2008) Apoptogenic activity of two benzophenanthridine alkaloids from Chelidonium majus L. does not correlate with their DNA damaging effects. Toxicol In Vitro 22:287–295

    CAS  PubMed  Google Scholar 

  • Pica F, Balestrieri E, Serafino A et al (2012) Antitumor effects of the benzophenanthridine alkaloid sanguinarine in a rat syngeneic model of colorectal cancer. Anticancer Drugs 23:32–42

    CAS  PubMed  Google Scholar 

  • Psotová J, Klejdus B, Večeřa R et al (2006a) A liquid chromatographic-mass spectrometric evidence of dihydrosanguinarine as a first metabolite of sanguinarine transformation in rat. J Chromatogr B 830:165–172

    Google Scholar 

  • Psotová J, Večeřa R, Zdařilová A, Anzenbacherová E et al (2006b) Safety assessment of sanguiritrin, alkaloid fraction of Macleaya cordata, in rats. Vet Med 51:145–155

    Google Scholar 

  • Reagan-Shaw S, Breur JN, Ahmad N (2006) Enhancement of UVB radiation-mediated apoptosis by sanguinarine in HaCaT human immortalized keratinocytes. Mol Cancer Ther 5:418–429

    Google Scholar 

  • Schmeller T, El-Shazly A, Wink M (1996) Allelochemical activities of pyrrolizidine alkaloids: interactions with neuroreceptors and acetylcholine related enzymes. J Chem Ecol 23:399–416

    Google Scholar 

  • Schmeller T, Latz-Brüning B, Wink M (1997) Biochemical activities of berberine, palmatine and sanguinarine mediating chemical defence against microorganisms and herbivores. Phytochemistry 44:257–266

    CAS  PubMed  Google Scholar 

  • Selvi BR, Pradhan SK, Shandilya J et al (2009) Sanguinarine interacts with chromatin, modulates epigenetic modifications, and transcription in the context of chromatin. Chem Biol 16:203–216

    Google Scholar 

  • Sen A, Maiti M (1994) Interaction of sanguinarine iminium and alkanolamine form with calf thymus DNA. Biochem Pharmacol 48:2097–2102

    CAS  PubMed  Google Scholar 

  • Sen A, Ray A, Maiti M (1996) Thermodynamics of the interactions of sanguinarine with DNA, influence of ionic strength and base composition. Biophys Chem 59:155–170

    CAS  PubMed  Google Scholar 

  • Serafim TL, Matos JAC, Sardao VA et al (2008) Sanguinarine cytotoxicity on mouse melanoma K1735–M2 cells: nuclear vs. mitochondrial effects. Biochem Pharm 76:1459–1475

    CAS  PubMed  Google Scholar 

  • Šimánek V, Vespalec R, Šedo A, Ulrichová J, Vičar J (2004) Quaternary benzo[c]phenanthridine alkaloids—biological activities. In: Schneider M (ed) Chemical probes in biology science at the interface of chemistry, biology and medicine. Springer, Netherlands, pp 245–254

    Google Scholar 

  • Slaninová I, Táborská E, Bochořáková H et al (2001) Interaction of benzo[c]phenanthridine and protoberberine alkaloids with animal and yeast cells. Cell Biol Toxicol 17:51–63

    PubMed  Google Scholar 

  • Slaninová I, Slanina J, Táborská E (2007a) Quaternary benzo[c]phenanthridine alkaloids - Novel cell permeant and red fluorescing DNA probes. Cytometry A 71:700–708

    PubMed  Google Scholar 

  • Slaninová I, Slunská Z, Šinkora J et al (2007b) Screening of minor benzo(c)phenanthridine alkaloids for anti-proliferative and apoptotic activities. Pharm Biol 45:131–139

    Google Scholar 

  • Slunská Z, Gelnarová E, Hammerová J et al (2010) Effect of quaternary benzo[c]phenanthridine alkaloids sanguilutine and chelilutine on normal and cancer cells. Toxicol In Vitro 24:697–706

    PubMed  Google Scholar 

  • Stiborová M, Simánek V, Frei E et al (2002) DNA adduct formation from quaternary benzo[c]phenanthridine alkaloids sanguinarine and chelerythrine as revealed by the P-32-postlabeling technique. Chem Biol Interact 140:231–242

    PubMed  Google Scholar 

  • Suchomelová J, Bochořáková H, Paulová H et al (2007) HPLC quantification of seven quaternary benzo[c]phenanthridine alkaloids in six species of the family Papaveraceae. J Pharm Biomed Anal 44:283–287

    PubMed  Google Scholar 

  • Sun M, Lou W, Chun JY et al (2010) Sanguinarine suppresses prostate tumor growth and inhibits survivin expression. Genes Cancer 1:283–292

    CAS  PubMed Central  PubMed  Google Scholar 

  • Táborský P, Slaninová I, Táborská E (2010) Quaternary benzo[c]phenanthridine alkaloids: Perspektive fluorescence DNA probes. In: Cassiano NM (ed) Alkaloids: properties, application and pharmacological effects. Nova Science Publishers Inc., New York, pp 81–89

    Google Scholar 

  • Tanahashi T, Zenk MH (1990) New hydroxylated benzo[c]phenanthridine alkaloids from Eschscholtzia californica cell suspension cultures. J Nat Prod 53:579–586

    CAS  PubMed  Google Scholar 

  • Toledo F, Wahl GM (2006) Regulating the p53 pathway: in vitro hypotheses, in vivo veritas. Nat Rev Cancer 6:909–923

    CAS  PubMed  Google Scholar 

  • Toyoda E, Kagaya S, Cowell IG et al (2008) NK314, a topoisomerase II inhibitor that specifically targets the alpha isoform. J Biol Chem 283:23711–23720

    CAS  PubMed  Google Scholar 

  • Ulrichová J, Dvořák Z, Fišar J et al (2001) Cytotoxicity of natural compounds in hepatocyte cell culture models. The case of quaternary benzo[c]phenanthridine alkaloids. Toxicol Lett 125:125–132

    PubMed  Google Scholar 

  • Urbanová J, Lubal P, Slaninová I et al (2008) Fluorescence properties of selected benzo[c]phenantridine alkaloids and studies of their interaction with CT DNA. Anal Bioanal Chem 394:997–1002

    Google Scholar 

  • Vacek J, Vrublová E, Kubala M et al (2011) Oxidation of sanguinarine and its dihydro-derivative at a pyrolytic graphite electrode using ex situ voltammetry. Study of the interactions of the alkaloids with DNA. Electroanalysis 23:1671–1680

    CAS  Google Scholar 

  • Vallejos RH, Rizzotto MG (1972) Effect of chelerythrine on mitochondrial energy coupling. FEBS Lett 21:195–198

    CAS  PubMed  Google Scholar 

  • Vandenabeele P, Galluzzi L, Vanden Berghe T et al (2010) Molecular mechanisms of necroptosis: an ordered cellular explosion. Nat Rev Mol Cell Biol 11:700–714

    CAS  PubMed  Google Scholar 

  • Vavrečková C, Gawlik I, Miller K (1996) Benzophenanthridine alkaloids of Chelidonium majus; inhibition of 5- and 12-lipoxygenase by a non-redox mechanism. Planta Med 62:397–401

    PubMed  Google Scholar 

  • Vespalec R, Barták P, Šimánek V et al (2003) Electrophoretic investigation of interactions of sanguinarine and chelerythrine with molecules containing mercapto group. J Chromatogr B 797:357–366

    CAS  Google Scholar 

  • Vogt A, Tamewitz A, Skoko J et al (2005) The benzo[c]phenanthridine alkaloid, sanguinarine, is a selective, cell-active inhibitor of mitogen-activated protein kinase phosphatase-1. J Biol Chem 280:19078–19086

    CAS  PubMed  Google Scholar 

  • Vrba J, Kosina P, Ulrichová J et al (2004) Involvement of cytochrome P450 1A in sanguinarine detoxication. Toxicol Lett 151:375–387

    CAS  PubMed  Google Scholar 

  • Vrba J, Doležel P, Vicar J et al (2008) Chelerythrine and dihydrochelerythrine induce G1 phase arrest and bimodal cell death in human leukemia HL-60 cells. Toxicol In Vitro 22:1008–1017

    CAS  PubMed  Google Scholar 

  • Vrba J, Doležel P, Vičar J et al (2009) Cytotoxic activity of sanguinarine and dihydrosanguinarine in human promyelocytic leukemia HL-60 cells. Toxicol In Vitro 23:580–588

    CAS  PubMed  Google Scholar 

  • Vrba J, Orolinová E, Ulrichová J (2012) Induction of heme oxygenase-1 by Macleaya cordata extract and its constituent sanguinarine in RAW264.7 cells. Fitoterapia 83:329–335

    CAS  PubMed  Google Scholar 

  • Wan KF, Chan SL, Sukumaran SK et al (2008) Chelerythrine induces apoptosis through a Bax/Bak-independent mitochondrial mechanism. J Biol Chem 283:8423–8433

    CAS  PubMed  Google Scholar 

  • Wang BH, Lu ZX, Polya GM (1997) Inhibition of eukaryote protein kinases by isoquinoline and oxazine alkaloids. Planta Med 63:494–498

    CAS  PubMed  Google Scholar 

  • Weerasinghe P, Hallock S, Tang SC et al (2001) Role of Bcl-2 family proteins and caspase-3 in sanguinarine-induced bimodal cell death. Cell Biol Toxicol 17:371–381

    CAS  PubMed  Google Scholar 

  • Williams MK, Dalvi S, Dalvi RR (2000) Influence of 3-methylcholanthrene pretreatment on sanguinarine toxicity in mice. Vet Hum Toxicol 42:196–198

    CAS  PubMed  Google Scholar 

  • Wolff J, Knipling L (1993) Antimicrotubule properties of benzophenanthridine alkaloids. Biochemistry 32:13334–13339

    CAS  PubMed  Google Scholar 

  • Yamamoto S, Seta K, Morisco C et al (2001) Chelerythrine rapidly induces apoptosis through generation of reactive oxygen species in cardiac myocytes. J Moll Cell Cardiol 33:1829–1848

    CAS  Google Scholar 

  • Yin HQ, Kim YH, Moon CK et al (2005) Reactive oxygen species-mediated induction of apoptosis by a plant alkaloid 6-methoxydihydrosanguinarine in HepG2 cells. Biochem Pharmacol 70(242):248

    Google Scholar 

  • Yousefi S, Simon HU (2009) Autophagy in cancer and chemotherapy. Results Probl Cell Differ 49:183–190

    CAS  PubMed  Google Scholar 

  • Zdařilová A, Malíková J, Dvořák Z et al (2006) Quaternary isoquinoline alkaloids sanguinarine and chelerythrine. In vitro and in vivo effects. Chem Listy 100:30–41

    Google Scholar 

  • Zhang YH, Bhunia A, Wan KF et al (2006) Chelerythrine and sanguinarine dock at distinct sites on Bcl [XL] that are not the classic BH3 binding cleft. J Mol Biol 364:536–549

    CAS  PubMed  Google Scholar 

  • Zhang ZF, Guo Y, Zhang JB et al (2011) Induction of apoptosis by chelerythrine chloride through mitochondrial pathway and Bcl-2 family proteins in human hepatoma SMMC-7721 Cell. Arch Pharm Res 34:791–800

    CAS  PubMed  Google Scholar 

  • Zhang Z, Guo Y, Zhang L et al (2012) Chelerythrine chloride from Macleaya cordata induces growth inhibition and apoptosis in human gastric cancer BGC-823 cells. Acta Pharm Sinica B 2:464–471

    CAS  Google Scholar 

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Acknowledgments

The work was supported by grants of Ministry of Education, Youth and Sports of the Czech Republic (KONTAKT II LH12176) and Masaryk University Projects of Specific Research MUNI/A/0798/2012 and MUNI/A/0818/2012.

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  1. Department of Biology, Faculty of Medicine, Masaryk University, Kamenice 5, Building A6, 62500, Brno, Czech Republic

    Iva Slaninová

  2. Department of Biochemistry, Faculty of Medicine, Masaryk University, Kamenice 5, Building A16, 62500, Brno, Czech Republic

    Kristýna Pěnčíková, Jana Urbanová, Jiří Slanina & Eva Táborská

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  1. Iva Slaninová
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  2. Kristýna Pěnčíková
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  3. Jana Urbanová
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Correspondence to Iva Slaninová.

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Slaninová, I., Pěnčíková, K., Urbanová, J. et al. Antitumour activities of sanguinarine and related alkaloids. Phytochem Rev 13, 51–68 (2014). https://doi.org/10.1007/s11101-013-9290-8

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  • DOI: https://doi.org/10.1007/s11101-013-9290-8

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