Phytochemistry Reviews

, Volume 13, Issue 1, pp 51–68 | Cite as

Antitumour activities of sanguinarine and related alkaloids

  • Iva Slaninová
  • Kristýna Pěnčíková
  • Jana Urbanová
  • Jiří Slanina
  • Eva Táborská


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.


Apoptosis Anti-proliferative activity Benzophenanthridine alkaloids Cancer Sanguinarine 



B-cell lymphoma 2 protein














Mitogen-activated protein kinase






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


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


Quaternary benzo[c]phenanthridine alkaloids


Reactive oxygen species








Tumour necrosis factor-related apoptosis-inducing ligand


Cyclin-dependent kinase


Dihydrofluorescein diacetate

DR4 5

Death receptor 4 and 5


Phosphorylated histone H2AX


Inhibitor of apoptosis


Matrix metalloproteinase-2 and 9


Receptor-interacting protein


Vascular endothelial growth factor



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.


  1. 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 74:548–552PubMedGoogle Scholar
  2. 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 9:3176–3182PubMedGoogle Scholar
  3. 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 3:933–940PubMedGoogle Scholar
  4. 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 889:54–63Google Scholar
  5. 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 6:1524–1528PubMedGoogle Scholar
  6. 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 249:198–208PubMedGoogle Scholar
  7. 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 83:986–993PubMedGoogle Scholar
  8. 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 138:173–183PubMedCentralPubMedGoogle Scholar
  9. 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 48:132–138PubMedGoogle Scholar
  10. Babu ChK, Khanna SK, Das M (2006) Safety evaluation studies on argemone oil through dietary exposure for 90 days in rats. Food Chem Toxicol 44:1151–1157PubMedGoogle Scholar
  11. 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 14:5439–5445PubMedGoogle Scholar
  12. 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 392:709–716PubMedGoogle Scholar
  13. Barreto MC, Pinto RE, Arrabaca JD et al (2003) Inhibition of mouse liver respiration by Chelidonium majus isoquinoline alkaloids. Toxicol Lett 146:37–47PubMedGoogle Scholar
  14. Basini G, Santini SE, Bussolati S et al (2007) The plant alkaloid sanguinarine is a potential inhibitor of follicular angiogenesis. J Reprod Dev 53:573–579PubMedGoogle Scholar
  15. 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 7:1109–1119PubMedGoogle Scholar
  16. Bhadra K, Kumar GS (2011) Interaction of berberine, palmatine, coralyne, and sanguinarine to quadruplex DNA: a comparative spectroscopic and calorimetric study. Biochim Biophys Acta 1810:485–496PubMedGoogle Scholar
  17. Booth NL, Sayers TJ, Brooks AD et al (2008) A cell-based high-throughput screen to identify synergistic TRAIL sensitizers. Cancer Immunol Immunother 58:1229–1244PubMedCentralPubMedGoogle Scholar
  18. Chan SL, Lee MC, Tan KO et al (2003) Identification of chelerythrine as an inhibitor of BclXL function. J Biol Chem 278:20453–20456PubMedGoogle Scholar
  19. 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 218:143–151PubMedGoogle Scholar
  20. 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 54:279–287PubMedGoogle Scholar
  21. 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 29:4457–4465PubMedGoogle Scholar
  22. 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 179:185–191PubMedGoogle Scholar
  23. Choi J, He N, Sung MK et al (2011) Sanguinarine is an allosteric activator of AMP-activated protein kinase. Biochem Biophys Res Commun 413:259–263PubMedGoogle Scholar
  24. 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 28:945–956PubMedGoogle Scholar
  25. 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 117:709–717PubMedGoogle Scholar
  26. De Stefano I, Raspaglio G, Zannoni GF et al (2009) Antiproliferative and antiangiogenic effects of the benzophenanthridine alkaloid sanguinarine in melanoma. Biochem Pharmacol 78:1374–1381PubMedGoogle Scholar
  27. 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 51:474–482PubMedGoogle Scholar
  28. Degterev A, Hitomi J, Germscheid M et al (2008) Identification of RIP1 kinase as a specific cellular target of necrostatins. Nat Chem Biol 4:313–321PubMedGoogle Scholar
  29. 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 52:391–397PubMedGoogle Scholar
  30. 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 63:1415–1421PubMedGoogle Scholar
  31. Dostál J, Slavík J (2002) Some aspects of the chemistry of quaternary benzo[c]phenanthridine alkaloids. Stud Nat Prod Chem 27:155–184Google Scholar
  32. 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 68:2403–2422Google Scholar
  33. Eun JP, Koh GY (2004) Suppression of angiogenesis by the plant alkaloid sanguinarine. Biochem Biophys Res Commun 317:618–624PubMedGoogle Scholar
  34. 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 87:1086–1091PubMedGoogle Scholar
  35. Funakoshi T, Aki T, Nakayama H et al (2011) Reactive oxygen species-independent rapid initiation of mitochondrial apoptotic pathway by chelerythrine. Toxicol In Vitro 25:1581–1587PubMedGoogle Scholar
  36. 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 6:1501–1508PubMedGoogle Scholar
  37. 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 80:321–327PubMedGoogle Scholar
  38. 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 62:22–35PubMedGoogle Scholar
  39. 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 393:647–658PubMedGoogle Scholar
  40. Han MH, Yoo YH, Choi YH (2008) Sanguinarine-induced apoptosis in human leukemia U937 cells via bcl-2 downregulation and caspase-3 activation. Chemotherapy 54:157–165PubMedGoogle Scholar
  41. Herbert JM, Augereau JM, Gleye J et al (1990) Chelerythrine is a potent and specific inhibitor of protein kinase C. Biochem Biophys Res Commun 172:993–999PubMedGoogle Scholar
  42. 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 117:3575–3784PubMedGoogle Scholar
  43. Holy J, Laminy G, Perkins E (2006) Disruption of nucleocytoplasmic trafficking of cyclin D1 and topoisomerase II by sanguinarine. BMC Cell Biol 7:13PubMedCentralPubMedGoogle Scholar
  44. Hossain M, Kumar GS (2009) DNA binding of benzophenanthridine compounds sanguinarine versus ethidium: comparative binding and thermodynamic profile of intercalation. J Chem Thermodyn 41:764–774Google Scholar
  45. 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 47:90–99Google Scholar
  46. Hussain AR, Al-Jomah NA, Siraj AK et al (2007) Sanguinarine-dependent induction of apoptosis in primary effusion lymphoma cells. Cancer Res 67:3888–3897PubMedGoogle Scholar
  47. 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 23:281–287PubMedGoogle Scholar
  48. 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 196:56–59PubMedGoogle Scholar
  49. 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 22:127–136PubMedCentralPubMedGoogle Scholar
  50. 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 1:2–15Google Scholar
  51. 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 177:168–181PubMedGoogle Scholar
  52. 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 32:271–277PubMedGoogle Scholar
  53. 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 158:50–60PubMedGoogle Scholar
  54. 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 237:67–75PubMedGoogle Scholar
  55. 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 104:895–907PubMedGoogle Scholar
  56. 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 42:85–91PubMedGoogle Scholar
  57. 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 879:1077–1085Google Scholar
  58. Kovář J, Stejskal J, Paulová H et al (1986) Reduction of quaternary benzophenanthridine alkaloids by NADH and NADPH. Collect Czech Chem Commun 51:2626–2634Google Scholar
  59. Lee SS, Kai M, Lee MK (2001) Inhibitory effects of sanguinarine on monoamine oxidase activity in mouse brain. Phytother Res 15:167–169PubMedGoogle Scholar
  60. 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 471:224–231PubMedGoogle Scholar
  61. 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 95:80–85Google Scholar
  62. Lopus M, Panda D (2006) The benzophenanthridine alkaloid sanguinarine perturbs microtubule assembly dynamics through tubulin binding. FEBS J 273:2139–2150PubMedGoogle Scholar
  63. 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 27:649–695PubMedGoogle Scholar
  64. Maiti M, Nandi R, Chaudhuri K (1982) Sanguinarine-a monofunctional intercalating alkaloid. FEBS Lett 142:280–284PubMedGoogle Scholar
  65. Maiti M, Nandi R, Chaudhuri K (1984) Interaction of sanguinarine with natural and synthetic deoxyribonucleic acids. Indian J Biochem Biol 21:158–165Google Scholar
  66. 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 22:439–453PubMedGoogle Scholar
  67. 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 172:63–71PubMedGoogle Scholar
  68. 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 477:43–52PubMedGoogle Scholar
  69. 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 70:37–46PubMedGoogle Scholar
  70. 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 1:985–988PubMedGoogle Scholar
  71. Nakanishi T, Suzuki M, Saimoto A et al (1999) Structural considerations of NK109, an antitumor benzo[c]phenanthridine alkaloid. J Nat Prod 62:864–867PubMedGoogle Scholar
  72. 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 10:2321–2323PubMedGoogle Scholar
  73. Newman DJ, Cragg GM (2012) Natural products as sources of new drugs over the 30 years from 1981 to 2010. J Nat Prod 75:311–335PubMedCentralPubMedGoogle Scholar
  74. Paulová H, Slavík J (1993) Interaction of sanguinarine with human serum-albumin. Pharmazie 48:555–556PubMedGoogle Scholar
  75. 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 19:890–895PubMedGoogle Scholar
  76. 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 22:287–295PubMedGoogle Scholar
  77. 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 23:32–42PubMedGoogle Scholar
  78. 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 830:165–172Google Scholar
  79. Psotová J, Večeřa R, Zdařilová A, Anzenbacherová E et al (2006b) Safety assessment of sanguiritrin, alkaloid fraction of Macleaya cordata, in rats. Vet Med 51:145–155Google Scholar
  80. Reagan-Shaw S, Breur JN, Ahmad N (2006) Enhancement of UVB radiation-mediated apoptosis by sanguinarine in HaCaT human immortalized keratinocytes. Mol Cancer Ther 5:418–429Google Scholar
  81. Schmeller T, El-Shazly A, Wink M (1996) Allelochemical activities of pyrrolizidine alkaloids: interactions with neuroreceptors and acetylcholine related enzymes. J Chem Ecol 23:399–416Google Scholar
  82. Schmeller T, Latz-Brüning B, Wink M (1997) Biochemical activities of berberine, palmatine and sanguinarine mediating chemical defence against microorganisms and herbivores. Phytochemistry 44:257–266PubMedGoogle Scholar
  83. 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 16:203–216Google Scholar
  84. Sen A, Maiti M (1994) Interaction of sanguinarine iminium and alkanolamine form with calf thymus DNA. Biochem Pharmacol 48:2097–2102PubMedGoogle Scholar
  85. Sen A, Ray A, Maiti M (1996) Thermodynamics of the interactions of sanguinarine with DNA, influence of ionic strength and base composition. Biophys Chem 59:155–170PubMedGoogle Scholar
  86. Serafim TL, Matos JAC, Sardao VA et al (2008) Sanguinarine cytotoxicity on mouse melanoma K1735–M2 cells: nuclear vs. mitochondrial effects. Biochem Pharm 76:1459–1475PubMedGoogle Scholar
  87. 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 245–254Google Scholar
  88. 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 17:51–63PubMedGoogle Scholar
  89. Slaninová I, Slanina J, Táborská E (2007a) Quaternary benzo[c]phenanthridine alkaloids - Novel cell permeant and red fluorescing DNA probes. Cytometry A 71:700–708PubMedGoogle Scholar
  90. Slaninová I, Slunská Z, Šinkora J et al (2007b) Screening of minor benzo(c)phenanthridine alkaloids for anti-proliferative and apoptotic activities. Pharm Biol 45:131–139Google Scholar
  91. 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 24:697–706PubMedGoogle Scholar
  92. 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 140:231–242PubMedGoogle Scholar
  93. 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 44:283–287PubMedGoogle Scholar
  94. Sun M, Lou W, Chun JY et al (2010) Sanguinarine suppresses prostate tumor growth and inhibits survivin expression. Genes Cancer 1:283–292PubMedCentralPubMedGoogle Scholar
  95. 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 81–89Google Scholar
  96. Tanahashi T, Zenk MH (1990) New hydroxylated benzo[c]phenanthridine alkaloids from Eschscholtzia californica cell suspension cultures. J Nat Prod 53:579–586PubMedGoogle Scholar
  97. Toledo F, Wahl GM (2006) Regulating the p53 pathway: in vitro hypotheses, in vivo veritas. Nat Rev Cancer 6:909–923PubMedGoogle Scholar
  98. Toyoda E, Kagaya S, Cowell IG et al (2008) NK314, a topoisomerase II inhibitor that specifically targets the alpha isoform. J Biol Chem 283:23711–23720PubMedGoogle Scholar
  99. 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 125:125–132PubMedGoogle Scholar
  100. 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 394:997–1002Google Scholar
  101. 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 23:1671–1680Google Scholar
  102. Vallejos RH, Rizzotto MG (1972) Effect of chelerythrine on mitochondrial energy coupling. FEBS Lett 21:195–198PubMedGoogle Scholar
  103. Vandenabeele P, Galluzzi L, Vanden Berghe T et al (2010) Molecular mechanisms of necroptosis: an ordered cellular explosion. Nat Rev Mol Cell Biol 11:700–714PubMedGoogle Scholar
  104. 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 62:397–401PubMedGoogle Scholar
  105. 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 797:357–366Google Scholar
  106. 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 280:19078–19086PubMedGoogle Scholar
  107. Vrba J, Kosina P, Ulrichová J et al (2004) Involvement of cytochrome P450 1A in sanguinarine detoxication. Toxicol Lett 151:375–387PubMedGoogle Scholar
  108. 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 22:1008–1017PubMedGoogle Scholar
  109. 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 23:580–588PubMedGoogle Scholar
  110. 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 83:329–335PubMedGoogle Scholar
  111. Wan KF, Chan SL, Sukumaran SK et al (2008) Chelerythrine induces apoptosis through a Bax/Bak-independent mitochondrial mechanism. J Biol Chem 283:8423–8433PubMedGoogle Scholar
  112. Wang BH, Lu ZX, Polya GM (1997) Inhibition of eukaryote protein kinases by isoquinoline and oxazine alkaloids. Planta Med 63:494–498PubMedGoogle Scholar
  113. 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 17:371–381PubMedGoogle Scholar
  114. Williams MK, Dalvi S, Dalvi RR (2000) Influence of 3-methylcholanthrene pretreatment on sanguinarine toxicity in mice. Vet Hum Toxicol 42:196–198PubMedGoogle Scholar
  115. Wolff J, Knipling L (1993) Antimicrotubule properties of benzophenanthridine alkaloids. Biochemistry 32:13334–13339PubMedGoogle Scholar
  116. 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 33:1829–1848Google Scholar
  117. 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):248Google Scholar
  118. Yousefi S, Simon HU (2009) Autophagy in cancer and chemotherapy. Results Probl Cell Differ 49:183–190PubMedGoogle Scholar
  119. Zdařilová A, Malíková J, Dvořák Z et al (2006) Quaternary isoquinoline alkaloids sanguinarine and chelerythrine. In vitro and in vivo effects. Chem Listy 100:30–41Google Scholar
  120. 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 364:536–549PubMedGoogle Scholar
  121. 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 34:791–800PubMedGoogle Scholar
  122. 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 2:464–471Google Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Iva Slaninová
    • 1
  • Kristýna Pěnčíková
    • 2
  • Jana Urbanová
    • 2
  • Jiří Slanina
    • 2
  • Eva Táborská
    • 2
  1. 1.Department of Biology, Faculty of MedicineMasaryk UniversityBrnoCzech Republic
  2. 2.Department of Biochemistry, Faculty of MedicineMasaryk UniversityBrnoCzech Republic

Personalised recommendations