New insights on the anticancer properties of dietary polyphenols

Medicinal Research Reviews

Volumn 26, Issue 6, 2006, Pages 747-766

  Fresco, P ^a   Borges, F ^a,b   Diniz, C ^a   Marques, M P M ^b,c  

^a UNIVERSITY OF PORTO   (Portugal)

^b UNIVERSITY OF COIMBRA   (Portugal)

^c UNIVERSITY OF COIMBRA   (Portugal)

Author keywords

Anticancer; Chemoprevention; Dietary polyphenols; Structure activity relationships

Indexed keywords

ANGIOGENESIS INHIBITOR; ANTIINFLAMMATORY AGENT; ANTIOXIDANT; BENZOIC ACID DERIVATIVE; CAFFEIC ACID; CAFFEIC ACID DERIVATIVE; CAPSAICIN; CINNAMIC ACID DERIVATIVE; COUMARIC ACID; COUMARIN DERIVATIVE; CURCUMIN; FERULIC ACID; FLAVONOID; GALLIC ACID; GALLIC ACID DERIVATIVE; GROWTH FACTOR RECEPTOR; HYDROXYBENZOIC ACID; HYDROXYBENZOIC ACID DERIVATIVE; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; LIGNAN DERIVATIVE; MITOGEN ACTIVATED PROTEIN KINASE; MUTAGENIC AGENT; POLYPHENOL DERIVATIVE; PROTEIN KINASE; PROTOCATECHUIC ACID; SINAPIC ACID; STILBENE DERIVATIVE; TANNIN DERIVATIVE; TRANSCRIPTION FACTOR AP 1; UNINDEXED DRUG;

ANTINEOPLASTIC ACTIVITY; APOPTOSIS; CANCER CELL; CANCER CONTROL; CANCER GROWTH; CANCER INCIDENCE; CANCER INHIBITION; CANCER SURGERY; CANCER THERAPY; CAUSE OF DEATH; CELL DEATH; CELL PROLIFERATION; CELL SURVIVAL; CHEMOPROPHYLAXIS; DIET; DIET SUPPLEMENTATION; DIETARY INTAKE; DRUG MECHANISM; DRUG STRUCTURE; FRUIT; GENE EXPRESSION; HUMAN; INFLAMMATION; MALIGNANT NEOPLASTIC DISEASE; ONCOLOGY; PRECANCER; PREVENTIVE MEDICINE; REVIEW; SIGNAL TRANSDUCTION; VEGETABLE;

ANTICARCINOGENIC AGENTS; ANTIOXIDANTS; APOPTOSIS; CELL CYCLE; DIET; FLAVONOIDS; HUMANS; NF-KAPPA B; PHENOLS;

EID: 33750958329     PISSN: 01986325     EISSN: None     Source Type: Journal    
DOI: 10.1002/med.20060     Document Type: Review

References (100)

1. Slaga TJ, Fisher SM, Weeks CE, Lein-Szanto AJP. Multistage carcinogenesis. In: Seije M, Bernstein IA, editors. Biochemistry of normal and abnormal epidermal differentiation. Tokyo: University of Tokyo Press; 1980. pp 19-38.
2. Pitot HC. Progression: the terminal stage in carcinogenesis. Jpn J Cancer Res 1989;80:599-607.
3. Stanley LA. Molecular aspects of chemical carcinogenesis: The roles of oncogenes and tumour suppressor genes. Toxicology 1995;96:173-194.
4. Morse MA, Stoner GD. Cancer chemoprevention: Principles and prospects. Carcinogenesis 1993;14: 1737-1746.
5. Kelloff GJ, Boone CW, Crowell JA, Nayfield SG, Hawk E, Malone WF, Steele VE, Lubet RA, Sigman CC. Risk biomarkers and current strategies for cancer chemoprevention. J Cell Biochem Suppl 1996;25: 1-14.
6. Kelloff GJ, Hawk ET, Karp JE, Crowell JA, Boone CW, Steele VE, Lubet RA, Sigman CC. Progress in clinical chemoprevention. Semin Oncol 1997;24:241-252.
7. Wattenberg LW. Chemoprevention of cancer. Cancer Res 1985;45:1-8.
8. Surh YJ. Cancer chemoprevention with dietary phytochemicals. Nat Rev Cancer 2003;3:768-780.
9. De Flora S. Mechanisms of inhibitors of mutagenesis and carcinogenesis. Mutat Res 1998;402:151-158.
10. Rao CV, Desai D, Rivenson A, Simi B, Amin S, Reddy BS. Chemoprevention of colon carcinogenesis by phenylethyl-3-methylcaffeate. Cancer Res 1995;55:2310-2315.
11. Tapiero H, Tew KD, Ba GN, Mathe G. Polyphenols: Do they play a role in the prevention of human pathologies? Biomed Pharmacother 2002;56:200-207.
12. Fiuza SM, Gomes C, Teixeira LJ, Girao da Cruz MT, Cordeiro MN, Milhazes N, Borges F, Marques MPM. Phenolic acid derivatives with potential anticancer properties-a structure-activity relationship study. Part 1: Methyl, propyl and octyl esters of caffeic and gallic acids. Bioorg Med Chem 2004;12:3581-3589.
13. Gomes CA, da Cruz TG, Andrade JL, Milhazes N, Borges F, Marques MPM. Anticancer activity of phenolic acids of natural or synthetic origin: A structure-activity study. J Med Chem 2003;46:5395-5401.
14. Mahmoud NN, Carothers AM, Grunberger D, Bilinski RT, Churchill MR, Martucci C, Newmark HL, Bertagnolli MM. Plant phenolics decrease intestinal tumors in an animal model of familial adenomatous polyposis. Carcinogenesis 2000;21:921-927.
15. Kelloff GJ. Perspectives on cancer chemoprevention research and drug development. Adv Cancer Res 2000;78:199-334.
16. Kong AN, Yu R, Hebbar V, Chen C, Owuor E, Hu R, Ee R, Mandlekar S. Signal transduction events elicited by cancer prevention compounds. Mutat Res 2001;480-481:231-241.
17. Yang F, Oz HS, Barve S, de Villiers WJ, McClain CJ, Varilek GW. The green tea polyphenol (-)-epigallocatechin-3-gallate blocks nuclear factor-κB activation by inhibiting I-κB kinase activity in the intestinal epithelial cell line IEC-6. Mol Pharmacol 2001;60:528-533.
18. Pan MH, Lin-Shiau SY, Ho CT, Lin JH, Lin JK. Suppression of lipopolysaccharide-induced nuclear factor-κB activity by theaflavin-3,3′-digallate from black tea and other polyphenols through down-regulation of I-κB kinase activity in macrophages. Biochem Pharmacol 2000;59:357-367.
19. Ahmad N, Gupta S, Mukhtar H. Green tea polyphenol epigallocatechin-3- gallate differentially modulates nuclear factor κB in cancer cells versus normal cells. Arch Biochem Biophys 2000;376:338-346.
20. Manna SK, Mukhopadhyay A, Aggarwal BB. Resveratrol suppresses TNF-induced activation of nuclear transcription factors NF-κB, activator protein-1, and apoptosis: Potential role of reactive oxygen intermediates and lipid peroxidation. J Immunol 2000;164:6509-6519.
21. Lo AH, Liang YC, Lin-Shiau SY, Ho CT, Lin JK. Carnosol, an antioxidant in rosemary, suppresses inducible nitric oxide synthase through down-regulating nuclear factor-κB in mouse macrophages. Carcinogenesis 2002;23:983-991.
22. Huang SC, Ho CT, Lin-Shiau SY, Lin JK. Carnosol inhibits the invasion of B16/F10 mouse melanoma cells by suppressing metalloproteinase-9 through down-regulating nuclear factor-kappa B and c-Jun. Biochem Pharmacol 2005;69:221-232.
23. Eferl R, Wagner EF. AP-1: A double-edged sword in tumorigenesis. Nat Rev Cancer 2003;3:859-868.
24. Kundu JK, Surh YJ. Molecular basis of chemoprevention by resveratrol: NF-κB and AP-1 as potential targets. Mutat Res 2004;555:65-80.
25. Halazonetis TD, Georgopoulos K, Greenberg ME, Leder P. c-Jun dimerizes with itself and with c-Fos, forming complexes of different DNA binding affinities. Cell 1988;55:917-924.
26. Karin M. The regulation of AP-1 activity by mitogen-activated protein kinases. J Biol Chem 1995; 270:16483-16486.
27. Yu R, Hebbar V, Kim DW, Mandlekar S, Pezzuto JM, Kong AN. Resveratrol inhibits phorbol ester and UV-induced activator protein 1 activation by interfering with mitogen-activated protein kinase pathways. Mol Pharmacol 2001;60:217-224.
28. Dong Z, Ma W, Huang C, Yang CS. Inhibition of tumor promoter-induced activator protein 1 activation and cell transformation by tea polyphenols, (-)-epigallocatechin gallate, and theaflavins. Cancer Res 1997;57:4414-4419.
29. Yoshioka K, Deng T, Cavigelli M, Karin M. Antitumor promotion by phenolic antioxidants: Inhibition of AP-1 activity through induction of Fra expression. Proc Natl Acad Sci USA 1995;92:4972-4976.
30. Kuo ML, Yang NC. Reversion of v-H-ras-transformed NIH 3T3 cells by apigenin through inhibiting mitogen activated protein kinase and its downstream oncogenes. Biochem Biophys Res Commun 1995;26:767-775.
31. Siddiqui IA, Adhami VM, Afaq F, Ahmad N, Mukhtar H. Modulation of phosphatidylinositol-3-kinase/protein kinase B- and mitogen-activated protein kinase-pathways by tea polyphenols in human prostate cancer cells. J Cell Biochem 2004;91:232-242.
32. Livneh E, Fishman DD. Linking protein kinase C to cell-cycle control. Eur J Biochem 1997;248:1-9.
33. Lin JK, Chen YC, Huang YT, Lin-Shiau SY. Suppression of protein kinase C and nuclear oncogene expression as possible molecular mechanisms of cancer chemoprevention by apigenin and curcumin. J Cell Biochem 1997;28-29(Suppl):39- 48.
34. Markovits J, Linassier C, Fosse P, Couprie J, Pierre J, Jacquemin-Sablon A, Saucier JM, Le Pecq JB, Larsen AK. Inhibitory effects of the tyrosine kinase inhibitor genistein on mammalian DNA topoisomerase II. Cancer Res 1989;49:5111-5117.
35. Liu JY, Lin SJ, Lin JK. Inhibitory effects of curcumin on protein kinase C activity induced by 12-O-tetradecanoyl-phorbol-13-acetate in NIH 3T3 cells. Carcinogenesis 1993;14:857-861.
36. Atten MJ, Attar BM, Milson T, Holian O. Resveratrol-induced inactivation of human gastric adenocarcinoma cells through a protein kinase C-mediated mechanism. Biochem Pharmacol 2001;62: 1423-1432.
37. Mendelsohn J, Baselga J. The EGF receptor family as targets for cancer therapy. Oncogene 2000;19:6550-6565.
38. Liang YC, Chen YC, Lin YL, Lin-Shiau SY, Ho CT, Lin JK. Suppression of extracellular signals and cell proliferation by the black tea polyphenol, theaflavin-3,3′-digallate. Carcinogenesis 1999;20:733-736.
39. Masuda M, Suzui M, Weinstein IB. Effects of epigallocatechin-3-gallate on growth, epidermal growth factor receptor signaling pathways, gene expression, and chemosensitivity in human head and neck squamous cell carcinoma cell lines. Clin Cancer Res 2001;7:4220-4229.
40. Masuda M, Suzui M, Lim JT, Deguchi A, Soh JW, Weinstein IB. Epigallocatechin-3-gallate decreases VEGF production in head and neck and breast carcinoma cells by inhibiting EGFR-related pathways of signal transduction. J Exp Ther Oncol 2002;2:350-359.
41. Liang YC, Lin-shiau SY, Chen CF, Lin JK. Suppression of extracellular signals and cell proliferation through EGF receptor binding by (-)-epigallocatechin gallate in human A431 epidermoid carcinoma cells. J Cell Biochem 1997;67:55-65.
42. Kaneuchi M, Sasaki M, Tanaka Y, Yamamoto R, Sakuragi N, Dahiya R. Resveratrol suppresses growth of Ishikawa cells through down-regulation of EGF. Int J Oncol 2003;23:1167-1172.
43. Palmieri L, Mameli M, Ronca G. Effect of resveratrol and some other natural compounds on tyrosine kinase activity and on cytolysis. Drugs Exp Clin Res 1999;25:79-85.
44. Korutla L, Kumar R. Inhibitory effect of curcumin on epidermal growth factor receptor kinase activity in A431 cells. Biochim Biophys Acta 1994;1224:597-600.
45. Levy J, Teuerstein I, Marbach M, Radian S, Sharoni Y. Tyrosine protein kinase activity in the DMBA-induced rat mammary tumor: Inhibition by quercetin. Biochem Biophys Res Commun 1984;123:1227-1233.
46. Semczuk A, Jakowicki JA. Alterations of pRb1-cyclin D1-cdk4/6-p16(INK4A) pathway in endometrial carcinogenesis. Cancer Lett 2004;203:1-12.
47. Gusman J, Malonne H, Atassi G. A reappraisal of the potential chemopreventive and chemotherapeutic properties of resveratrol. Carcinogenesis 2001;22:1111-1117.
48. Liang YC, Lin-Shiau SY, Chen CF, Lin JK, Inhibition of cyclin-dependent kinases 2 and 4 activities as well as induction of Cdk inhibitors p21 and p27 during growth arrest of human breast carcinoma cells by (-)-epigallocatechin-3- gallate. J Cell Biochem 1999;75:1-12.
49. Salomon DS, Brandt R, Ciardiello F, Normanno N. Epidermal growth factor-related peptides and their receptors in human malignancies. Crit Rev Oncol Hematol 1995;19:183-232.
50. Suh N, Luyengi L, Fong HH, Kinghorn AD, Pezzuto JM. Discovery of natural product chemopreventive agents utilizing HL-60 cell differentiation as a model. Anticancer Res 1995;15:233-239.
51. Chen JH, Shao Y, Huang MT, Chin CK, Ho CT. Inhibitory effect of caffeic acid phenethyl ester on human leukemia HL-60 cells. Cancer Lett 1996;108:211-214.
52. Surh YJ, Hurh YJ, Kang JY, Lee E, Kong G, Lee SJ. Resveratrol, an antioxidant present in red wine, induces apoptosis in human promyelocytic leukemia (HL-60) cells. Cancer Lett 1999;140:1-10.
53. Leu TH, Maa MC. The molecular mechanisms for the antitumorigenic effect of curcumin. Curr Med Chem Anti-Canc Agents 2002;2:357-370.
54. Jiang MC, Yang-Yen HF, Yen JJ, Lin JK. Curcumin induces apoptosis in immortalized NIH 3T3 and malignant cancer cell lines. Nutr Cancer 1996;26:111-120.
55. Kuo PL, Chiang LC, Lin CC. Resveratrol-induced apoptosis is mediated by p53-dependent pathway in Hep G2 cells. Life Sci 2002;72:23-34.
56. Dorrie J, Gerauer H, Wachter Y, Zunino SJ. Resveratrol induces extensive apoptosis by depolarizing mitochondrial membranes and activating caspase-9 in acute lymphoblastic leukemia cells. Cancer Res 2001;61:4731-4739.
57. Tsan MF, White JE, Maheshwari JG, Bremner TA, Sacco J. Resveratrol induces Fas signaling-independent apoptosis in THP-1 human monocytic leukaemia cells. Br J Haematol 2000;109:405-412.
58. Hsu S, Singh B, Schuster G. Induction of apoptosis in oral cancer cells: Agents and mechanisms for potential therapy and prevention. Oral Oncol 2004;40:461-473.
59. Yang GY, Liao J, Kim K, Yurkow EJ, Yang CS. Inhibition of growth and induction of apoptosis in human cancer cell lines by tea polyphenols. Carcinogenesis 1998;19:611-616.
60. D'Alessandro T, Prasain J, Benton MR, Botting N, Moore R, Darley-Usmar V, Patel R, Barnes S. Polyphenols, inflammatory response, and cancer prevention: Chlorination of isoflavones by human neutrophils. J Nutr 2003;133:3773S-3777S.
61. Ruffin MT IV, Rock CL. Do antioxidants still have a role in the prevention of human cancer? Curr Oncol Rep 2001;3:306-313.
62. Kovacic P, Jacintho JD. Mechanisms of carcinogenesis: Focus on oxidative stress and electron transfer. Curr Med Chem 2001;8:773-796.
63. Lin JK, Shih CA. Inhibitory effect of curcumin on xanthine dehydrogenase/oxidase induced by phorbol-12-myristate-13-acetate in NIH3T3 cells. Carcinogenesis 1994;15:1717-1721.
64. Zhang F, Altorki NK, Mestre JR, Subbaramaiah K, Dannenberg AJ. Curcumin inhibits cyclooxygenase-2 transcription in bile acid- and phorbol ester-treated human gastrointestinal epithelial cells. Carcinogenesis 1999;20:445-451.
65. Hong J, Smith TJ, Ho CT, August DA, Yang C. Effects of purified green and black tea polyphenols on cyclooxygenase- and lipoxygenase-dependent metabolism of arachidonic acid in human colon mucosa and colon tumor tissues. Biochem Pharmacol 2001;62:1175-1183.
66. Le Corre L, Chalabi N, Delort L, Bignon YJ, Bernard-Gallon DJ. Resveratrol and breast cancer chemoprevention: Molecular mechanisms. Mol Nutr Food Res 2005;49:462-471.
67. Fiander H, Schneider H. Dietary ortho polyphenols that induce glutathione S-transferase and increase the resistance of cells to hydrogen peroxide are potential cancer chemopreventives that act by two mechanisms: The alleviation of oxidative stress and the detoxification of mutagenic xenobiotics. Cancer Lett 2000;156:117-124.
68. Chen C, Kong NA. Dietary chemopreventive compounds and ARE/EpRE signaling. Free Radic Biol Med 2004;36:1505-1516.
69. Gourley M, Williamson JS. Angiogenesis: New targets for the development of anticancer chemotherapies. Curr Pharm Des 2000;6:417-439.
70. Tan WF, Lin LP, Li MH, Zhang YX, Tong YG, Xiao D, Ding J. Quercetin, a dietary-derived flavonoid, possesses antiangiogenic potential. Eur J Pharmacol 2003;459:255-262.
71. Lin MT, Yen ML, Lin CY, Kuo ML. Inhibition of vascular endothelial growth factor-induced angiogenesis by resveratrol through interruption of Src-dependent vascular endothelial cadherin tyrosine phosphorylation. Mol Pharmacol 2003;64:1029-1036.
72. Fang MZ, Wang Y, Ai N, Hou Z, Sun Y, Lu H, Welsh W, Yang CS. Tea polyphenol (-)-epigallocatechin-3-gallate inhibits DNA methyltransferase and reactivates methylation-silenced genes in cancer cell lines. Cancer Res 2003;63:7563-7570.
73. Berger SJ, Gupta S, Belfi CA, Gosky DM, Mukhtar H. Green tea constituent (-)-epigallocatechin-3-gallate inhibits topoisomerase I activity in human colon carcinoma cells. Biochem Biophys Res Commun 2001;288:101-105.
74. Naasani I, Oh-Hashi F, Oh-Hara T, Feng WY, Johnston J, Chan K, Tsuruo T. Blocking telomerase by dietary polyphenols is a major mechanism for limiting the growth of human cancer cells in vitro and in vivo. Cancer Res 2003;63:824-830.
75. Ferrero ME, Bertelli AA, Pellegatta F, Fulgenzi A, Corsi MM, Bertelli A. Phytoalexin resveratrol (3-4′-5-trihydroxystilbene) modulates granulocyte and monocyte endothelial adhesion. Transplant Proc 1998;30:4191-4193.
76. Mitchell SH, Zhu W, Young CY. Resveratrol inhibits the expression and function of the androgen receptor in LNCaP prostate cancer cells. Cancer Res 1999;59:5892-5895.
77. Lee YJ, Liao PH, Chen WK, Yang CY. Preferential cytotoxicity of caffeic acid phenethyl ester analogues on oral cancer cells. Cancer Lett 2000;153:51-56.
78. van Zanden JJ, Geraets L, Wortelboer HM, van Bladeren PJ, Rietjens IM, Cnubben NH. Structural requirements for the flavonoid-mediated modulation of glutathione S-transferase P1-1 and GS-X pump activity in MCF7 breast cancer cells. Biochem Pharmacol 2004;67:1607-1617.
79. Farkas O, Jakus J, Héberger K. Quantitative structure-antioxidant activity relationships of flavonoid compounds. Molecules 2004;9:1079-1088.
80. Thakur A, Vishwakarma S, Thakur M. QSAR study of flavonoid derivatives as p56lck tyrosinkinase inhibitors. Bioorg Med Chem 2004;12:1209-1214.
81. Imai K, Suga K, Nakachi K. Cancer-preventive effects of drinking green tea among a Japonese population. Prev Med 1997;26:769-775.
82. Chauhan DP. Chemotherapeutic potential of curcumin for colorectal cancer. Curr Pharm Des 2002;8: 1695-1706.
83. Galati G, O'Brien P. Potential toxicity of flavonoids and other dietary phenolics: Significance for their chemopreventive and anticancer properties. Free Radic Biol Med 2004;37:287-303.
84. Cao G, Sofic E, Prior RL. Antioxidant and prooxidant behaviour of flavonoids: Structure-activity relationships. Free Radic Biol Med 1997;22:749-760.
85. Serrano A, Palacios C, Roy G, Cespon C, Villar ML, Nocito M, Gonzalez-Porque P. Derivatives of gallic acid induce apoptosis in tumoral cell lines and inhibit lymphocyte proliferation. Arch Biochem Biophys 1998;350:49-54.
86. Kampa M, Alexaki VI, Notas G, Nifli AP, Nistikaki A, Hatzoglou A, Bakogeorgou E, Kouimtzoglou E, Blekas G, Boskou D, Gravanis A, Castanas E. Antiproliferative and apoptotic effects of selective phenolic acids on T47D human breast cancer cells: Potential mechanisms of action. Breast Cancer Res 2004;6:R63-R74.
87. Taraphdar AK, Roy M, Bhattacharya RK. Natural products as inducers of apoptosis: Implication for cancer therapy and prevention. Curr Science 2001;80:1387-1396.
88. Lee YT, Don MJ, Hung PS, Shen YC, Lo YS, Chang KW, Chen CF, Ho LK. Cytotoxicity of phenolic acid phenethyl esters on oral cancer cells. Cancer Lett 2005;223:19-25.
89. Surh YJ. Molecular mechanisms of chemopreventive effects of selected dietary and medicinal phenolic substances. Mutat Res 1999;428:305-327.
90. Chung WY, Jung YJ, Surh YJ, Lee SS, Park KK. Antioxidative and antitumor promoting effects of [6]-paradol and its homologs. Mutat Res 2001;496:199-206.
91. Bode AM, Dong Z. Targeting signal transduction pathways by chemopreventive agents. Mutat Res 2004;555:33-51.
92. Petersen M, Simmonds MS. Rosmarinic acid. Phytochemistry 2003;62:121-125.
93. Babich H, Visioli F. In vitro cytotoxicity to human cells in culture of some phenolics from olive oil. Farmaco 2003;58:403-407.
94. Ren W, Qiao Z, Wang H, Zhu L, Zhang L. Flavonoids: Promising anticancer agents. Med Res Rev 2003;3:519-534.
95. Cipak L, Rauko P, Miadokova E, Cipakova I, Novotny L. Effects of flavonoids on cisplatin-induced apoptosis of HL-60 and L1210 leukemia cells. Leuk Res 2003;27:65-72.
96. Wang J, Mazza G. Effects of anthocyanins and other phenolic compounds on the production of tumor necrosis factor alpha in LPS/IFN-gamma-activated RAW 264.7 macrophages. J Agric Food Chem 2002;50:4183-4189.
97. Hou DX, Fujii M, Terahara N, Yoshimoto M. Molecular mechanisms behind the chemopreventive effects of anthocyanidins. J Biomed Biotechnol 2004;2004:321-325.
98. Singh RP, Tyagi AK, Zhao J, Agarwal R. Silymarin inhibits growth and causes regression of established skin tumors in SENCAR mice via modulation of mitogen-activated protein kinases and induction of apoptosis. Carcinogenesis 2002;23:499-510.
99. Borges F, Roleira F, Milhazes N, Santana L, Uriarte E. Simple coumarins and analogues in medicinal chemistry: Occurrence, synthesis and biological activity. Curr Med Chem 2005;12:887-916.
100. Hibasami H, Fujikawa T, Takeda H, Nishibe S, Satoh T, Fujisawa T, Nakashima K. Induction of apoptosis by Acanthopanax senticosus HARMS and its component, sesamin in human stomach cancer KATO III cells. Oncol Rep 2000;7:1213-1216.