A flavonoid antioxidant, silymarin, affords exceptionally high protection against tumor promotion in the SENCAR mouse skin tumorigenesis model

Cancer Research

Volumn 59, Issue 3, 1999, Pages 622-632

  Lahiri Chatterjee, Moushumi ^a   Katiyar, Santosh K ^a   Mohan, Rajiv R ^a   Agarwal, Rajesh ^a,b,c,d  

^a CASE WESTERN RESERVE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY HOSPITALS OF CLEVELAND   (United States)

^c UNIVERSITY OF COLORADO   (United States)

^d UNIVERSITY OF COLORADO CANCER CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

SILYMARIN;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER INHIBITION; CANCER PREVENTION; DRUG EFFECT; DRUG POTENCY; FEMALE; MOUSE; NONHUMAN; OXIDATION REDUCTION REACTION; PRIORITY JOURNAL; SKIN CANCER;

ANIMALS; ANTICARCINOGENIC AGENTS; ANTIOXIDANTS; CARCINOGENS; CELL DIVISION; DNA; EDEMA; FEMALE; HYPERPLASIA; LIPID PEROXIDATION; MICE; MICE, INBRED SENCAR; SILYMARIN; SKIN; SKIN NEOPLASMS; TETRADECANOYLPHORBOL ACETATE;

EID: 0033082440     PISSN: 00085472     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (74)

1. Cancer Facts and Figures: 1997. American Cancer Society, Inc., 1997.
2. Kelloff, G. J., Boone, C. W., Crowell, J. A., Steele, V. E., Lubet, R., and Sigman C. C. Chemopreventive drug development: prospectives and progress. Cancer Epidemiol. Biomarkers Prev., 3: 85-98, 1994.
3. Kelloff, G. J., Boone, C. W., Crowell, J. A., Nayfield, S. G., Hawk, E., Malone, W. F., Steele, V. E., Lubet, R. A., and Sigman, C. C. Risk biomarkers and current strategies for cancer chemoprevention. J. Cell. Biochem., 25S: 1-14, 1996.
4. Birt, D. F., Pelling, J. C., Nair, S., and Lepley, D. Diet intervention for modifying cancer risk. Prog. Clin. Biol. Res., 395: 223-234, 1996.
5. Morse, M. A., and Stoner, G. D. Cancer chemoprevention: principles and prospects. Carcinogenesis (Lond.), 14: 1737-1746, 1993.
6. Lipkin, M. New rodent models for studies of chemopreventive agents. J. Cell. Biochem. Suppl., 29: 144-147, 1997.
7. Conney, A. H., Lou, Y. R., Xie, J. G., Osawa, T., Newmark, H. L., Liu, Y., Chang, R. L., and Huang, M. T. Some perspectives on dietary inhibition of carcinogenesis: studies with curcumin and tea. Proc. Soc. Exp. Biol. Med., 216: 234-245, 1997.
8. Goodman, G. E. The clinical evaluation of cancer prevention agents. Proc. Soc. Exp. Biol. Med., 216: 253-259, 1997.
9. Boone, C. W., Bacus, J. W., Bacus, J. V., Steele, V. E., and Kelloff, G. J. Properties of intraepithelial neoplasia relevant to the development of cancer chemopreventive agents. J. Cell. Biochem. Suppl., 28: 1-20, 1997.
10. Hong, W. K., and Sporn, M. B. Recent advances in chemoprevention of cancer. Science (Washington DC), 278: 1073-1077, 1997.
11. Wattenberg, L. W. An overview of chemoprevention: current status and future prospects Proc. Soc. Exp. Biol. Med., 216: 133-141, 1997.
12. Perchellet, J-P., and Perchellet, E. M. Antioxidants and multistage carcinogenesis in mouse skin. Free Radical Biol. Med., 7: 377-408, 1989.
13. Dragsted, L. O. Natural antioxidants in chemoprevention. Arch. Toxicol. Suppl., 20: 209-226, 1998.
14. Mukhtar, H., and Agarwal, R. Skin cancer chemoprevention. J. Invest. Dermatol. Symp. Proc., 1: 209-214, 1996.
15. Mereish, K. A., Bunner, D. L., Ragland, D. R., and Creasia, D. A. Protection against microcystin-LR-induced hepatotoxicity by silymarin: biochemistry, histopathology, and lethality. Pharm. Res., 8: 273-277, 1991.
16. Letteron, P., Labbe, G., Degott, C., Berson, A., Fromenty, B., Delaforge, M., Larrey, D., and Pessayre, D. Mechanism for the protective effects of silymarin against carbon tetrachloride-induced lipid peroxidation and hepatotoxicity in mice. Biochem. Pharmacol., 39: 2027-2034, 1990.
17. Ferenci, P., Dragosics, B., Dittrich, H., Frank, H., Benda, L., Lochs, H., Meryn, S., Base, W., and Schneider, B. Randomized controlled trial of silymarin treatment in patients with cirrhosis of the liver. J. Hepatol., 9: 105-113, 1989.
18. 4-induced liver cirrhosis by silymarin. Fund. Clin. Pharmacol., 3: 183-191, 1989.
19. Vogel, G., Trost, W., and Braatz, R. Studies on the pharmacodynamics, including site and mode of action, of silymarin: the antihepatotoxic principle from Silybum marianum (L) Caertn. Arzneim. Forsch., 25: 82-89, 1975.
20. Hahn, V. G., Lehmann, H. D., Kurten, M., Uebel, H., and Vogel, G. Pharmacology and toxicology of silymarin, the anti-hepatotoxic agent of Silybum marianum (L.) Gaertn. Arzneim. Forsch., 18: 698-704, 1968.
21. Ely, H. Dermatologic therapies you've probably never heard of. Dermatol. Clin., 7: 19-35, 1989.
22. Wagner, H., Seligmann, O., Horhammer, L., and Munster, R. The chemistry of silymarin (silybin), the active principle of the fruits of Silybum marianum (L). Gaertn. (Carduus marianus) (L). Arzneim. Forsch., 18: 688-696, 1968.
23. Bosisio, E., Benelli, C., and Pirola, O. Effect of the flavanolignans of Silybum marianum L. on lipid peroxidation in rat liver microsomes and freshly isolated hepatocytes. Pharmacol. Res., 25: 147-154, 1992.
24. Carini, R., Comoglio, A., Albano, E., and Poli, G. Lipid peroxidation and irreversible damage in the rat hepatocyte model. Protection by the silybin-phospholipid complex IdB 1016. Biochem. Pharmacol., 43: 2111-2115, 1992.
25. Racz, K., Feher, J., Csomos, G., Varga, I., Kiss, R., and Glaz, E. An antioxidant drug, silibinin, modulates steroid secretion in human pathological adrenocortical cells. J. Endocrinol., 124: 341-345, 1990.
26. Valenzuela, A., Guerra, R., and Videla, L. A. Antioxidant properties of the flavonoids silybin and (+)-cyanidanol-3: comparison with butylated hydroxyanisole and butylated hydroxytoluene. Planta Med., 5: 438-440, 1986.
27. Comoglio, A., Leonarduzzi, G., Carini, R., Busolin, D., Basaga, H., Albano, E., Tomasi, A., Poli, G., Morazzoni, P., and Magistretti, M. J. Studies on the antioxidant and free radical scavenging properties of IdB1016 a new flavanolignan complex. Free Radical Res. Commun. 11: 109-115, 1990.
28. Muzes, G., Deak, G., Lang, I., Nekam, K., Gergely, P., and Feher, J. Effect of the bioflavonoid silymarin on the in vitro activity and expression of superoxide dismutase (SOD) enzyme. Acta Physiol. Hung., 78: 3-9, 1991.
29. Steele, V. E., Kelloff, G. J., Wilkinson, B. P., and Arnold, J. T. Inhibition of transformation in cultured rat tracheal epithelial cells by potential chemopreventive agents. Cancer Res., 50: 2068-2074, 1990.
30. Rudd, C. J., Suing, K. D., Pardo, K., and Kelloff, G. Evaluation of potential chemopreventive agents using a mouse epidermal cell line, JB6. Proc. Am. Assoc. Cancer Res., 31: 127, 1990.
31. Mehta, R. G., and Moon, R. C. Characterization of effective chemopreventive agents in mammary gland in vitro using an initiation-promotion protocol. Anticancer Res., 11: 593-596, 1991.
32. Agarwal, R., Katiyar, S. K., Lundgren, D. W., and Mukhtar, H. Inhibitory effect of silymarin, an anti-hepatotoxic flavonoid, on 12-O-tetradecanoylphorbol-13-acetate-induced epidermal ornithine decarboxylase activity and mRNA in SENCAR mice. Carcinogenesis (Lond.), 15: 1099-1103, 1994.
33. Katiyar, S. K., Korman, N. J., Mukhtar, H., and Agarwal, R. Protective effects of silymarin against photocarcinogenesis in mouse skin model. J. Natl. Cancer Inst. (Bethesda), 89: 556-566, 1997.
34. Zi, X., Mukhtar, H., and Agarwal, R. Novel cancer chemopreventive effects of a flavonoid antioxidant silymarin: inhibition of mRNA expression of an endogenous tumor promoter TNFα. Biochem. Biophys. Res. Commun., 239: 334-339, 1997.
35. Fujiki, H., Sueoka, E., Komori, A., and Suganuma, M. Tumor promotion and TNF-α gene expression by the okadaic acid class tumor promoters. Environ. Carcinog. Ecotoxicol. Rev., C15: 1-40, 1997.
36. Boutwell, R. K. Some biological aspects of skin carcinogenesis. Prog. Exp. Tumor Res., 4: 207-250, 1964.
37. Slaga, T. J., Fischer, S. M., Nelson, K., and Gleason, G. L. Studies on the mechanism of skin tumor promotion: evidence for several stages in promotion. Proc. Natl. Acad. Sci. USA, 77: 3659-3663, 1980.
38. Slaga, T. J. Overview of tumor promotion in animals. Environ. Health Perspect., 50: 3-14, 1983.
39. Furstenberger, G., Berry, D. L., Sorg, B., and Marks, F. Skin tumor promotion by phorbol esters is a two-stage process. Proc. Natl. Acad. Sci. USA, 78: 7722-7726, 1981.
40. Furstenberger, G., Sorg, B., and Marks, F. Skin tumor promotion by phorbol esters in skin: evidence for a memory effect. Science (Washington DC), 220: 89-91, 1983.
41. Agarwal, R., and Mukhtar, H. Cutaneous chemical carcinogenesis. In: H. Mukhtar (ed.), Pharmacology of the Skin, pp. 371-387. Boca Raton, FL: CRC Press, 1991.
42. DiGiovanni, J. Multistage carcinogenesis in mouse skin. Pharmacol. Ther., 54: 63-128, 1992.
43. Yuspa, S. H. The pathogenesis of squamous cell cancer: lessons learned from studies of skin carcinogenesis: thirty-third G. H. A. Clowes Memorial Award Lecture. Cancer Res., 54: 1178-1189, 1994.
44. Verma, A. K. Inhibition of both stage I and stage II mouse skin tumor promotion by retinoic acid and the dependence of inhibition of tumor promotion on the duration of retinoic acid treatment. Cancer Res., 47: 5097-5101, 1987.
45. Katiyar, S. K., Agarwal, R., and Mukhtar, H. Inhibition of both stage I and stage II skin tumor promotion in SENCAR mice by a polyphenolic fraction isolated from green tea: inhibition depends on the duration of polyphenol treatment. Carcinogenesis (Lond.), 14: 2641-2643, 1993.
46. Agarwal, R., Wang, Z. Y., Bik, D. P., and Mukhtar, H. Nordihydroguaiaretic acid, an inhibitor of lipoxygenase, also inhibits cytochrome P450-mediated monooxygenase activity in rat epidermal and hepatic microsomes. Drug Metab. Disp., 19: 620-624, 1991.
47. Wright, J. R., Colby, H. D., and Miles, P. R. Cytosolic factors which affect microsomal lipid peroxidation in lung and liver. Arch. Biochem. Biophys., 206: 296-304, 1981.
48. Katiyar, S. K., Agarwal, R., and Mukhtar, H. Inhibition of spontaneous and photo-enhanced lipid peroxidation in mouse epidermal microsomes by epicatechin derivatives from green tea. Cancer Lett., 79: 61-66, 1994.
49. Katiyar, S. K., Agarwal, R., Wood, G. S., and Mukhtar, H. Inhibition of 12-O-tetradecanoylphorbol-13-acetate-caused tumor promotion in 7,12-dimethylbenz[a]anthracene-initiated SENCAR mouse skin by a polyphenolic fraction isolated from green tea. Cancer Res., 52: 6890-6897, 1992.
50. Cerutti, P. A. Oxy-radicals and cancer. Lancet, 344: 862-863, 1994.
51. Kensler, T. W., and Taffe, B. G. Role of free radicals in tumor promotion and progression. Prog. Clin. Biol. Res., 298: 233-248, 1989.
52. Perchellet, E. M., and Perchellet, J. P. Characterization of the hydroperoxide response observed in mouse skin treated with tumor promoters in vivo. Cancer Res., 49: 6193-6201, 1989.
53. Park, J. W., and Floyd, R. A. Lipid peroxidation products mediate the formation of 8-hydroxydeoxyguanosine in DNA. Free Radical Biol. Med., 12: 245-250, 1992.
54. Girotti, A. W. Mechanisms of lipid peroxidation. J. Free Radical Biol. Med., 1: 87-95, 1985.
55. Ames, B. N., Gold, L. S., and Willett, W. C. The causes and prevention of cancer. Proc. Natl. Acad. Sci. USA, 92: 5258-5265, 1995.
56. Agarwal, R., Katiyar, S. K., Zaidi, S. I. A., and Mukhtar, H. Inhibition of skin tumor promoter-caused induction of epidermal ornithine decarboxylase in SENCAR mice by polyphenolic fraction isolated from green tea and its individual epicatechin derivatives. Cancer Res., 52: 3582-3588, 1992.
57. Yang, C. S., and Wang, Z. Y. Tea and cancer. J. Natl. Cancer Inst. (Bethesda), 85: 1038-1049, 1993.
58. Dong, Z., Ma, W., Huang, C., and Yang, C. S. Inhibition of tumor promoter-induced activator protein 1 activation and cell transformation by tea polyphenols. (-)-epigallocatechin gallate, and theaflavins. Cancer Res., 57: 4414-4419, 1997.
59. Zi, X., and Agarwal, R. Arti-proliferative and apoptotic effects of a potent cancer preventive agent silymarin are mediated via distinct signals involving respectively ERK and JNK pathways. Proc. Am. Assoc. Cancer Res., 39: 291, 1998.
60. Agarwal, R., and Mukhtar, H. Oxidative stress in skin chemical carcinogenesis. In: J. Fuchs and L. Packer (eds.), Oxidative Stress in Dermatology, pp. 207-241. New York: Marcel Dekker, Inc., 1993.
61. Fischer, S. M., Baldwin, J. K., Jasheway, D. W., Patrick, K. E., and Cameron, G. S. Phorbol ester induction of 8-lipoxygenase in inbred SENCAR (SSIN) but not C57BL/6J mice correlated with hyperplasia, edema, and oxidant generation but not ornithine decarboxylase induction. Cancer Res., 48: 658-664, 1988.
62. Katiyar, S. K., Rupp. C. O., Korman, N. J., Agarwal, R., and Mukhtar, H. Inhibition of 12-O-tetradecanoylphorbol-13-acelate and other skin tumor promoter-caused induction of epidermal interleukin-1a mRNA and protein expression in SENCAR mice by green tea polyphenols. J. Invest. Dermatol., 105: 394-398, 1995.
63. Imamoto, A., Beltran, L. M., and DiGiovanni, J. Evidence for autocrine/paracrine growth stimulation by transforming growth factor-α during the process of skin tumor promotion. Mol. Carcinog., 4: 52-60, 1991.
64. Kiguchi, K., Beltran, L. M., You, J., Rho, O., and DiGiovanni, J. Diverse tumor promoters elevate expression of transforming growth factor-α mRNA and protein in SENCAR mouse epidermis. Mol. Carcinog., 12: 225-235, 1995.
65. Finzi, E., Kilkenny, A., Strickland, J. E., Balaschak, M., Bringman, T., Derynck, R., Aaronson, S., and Yuspa, S. TGF α stimulates growth of skin papillomas by autocrine and paracrine mechanisms but does not cause neoplastic progression. Mol. Carcinog., 1: 7-12, 1988.
66. Dominey, A. M., Wang, X-J., King, L. E., Nanney, L. B., Gagne, T. A., Sellheyer, K., Bundman, D. S., Longley, M. A., Rothnagel, J. A., Greenhalgh, D. A., and Roop, D. R. Targeted over-expression of transforming growth factor-α in the epidermis of transgenic mice elicits hyperplasia, hyperkeratosis, and spontaneous squamous papillomas. Cell Growth Differ., 4: 1071-1082, 1993.
67. Rho, O., Beltran, L. M., Gimenez-Conti, I. B., and DiGiovanni, J. Altered expression of the epidermal growth factor receptor and transforming growth factor-α during multistage skin carcinogenesis in SENCAR mice. Mol. Carcinog., 11: 19-28, 1994.
68. Xian, W., Kiguchi, K., Imamoto, A., Rupp, T., Zilberstein, A., and DiGiovanni, J. Activation of the epidermal growth factor receptor by skin tumor promoters and in skin tumors from SENCAR mice. Cell Growth Differ., 6: 1447-1455, 1995.
69. Glick, A. B., Kulkami, A. B., Tennenbaum, T., Hennings, H., Flandars, K. C., O'Reilly, M., Sporn, M. B., Karlsson, S., and Yuspa, S. H. Loss of expression of transforming growth factor β in skin and skin tumors is associated with hyperproliferation and a high risk for malignant conversion. Proc. Natl. Acad. Sci. USA, 90: 6076-6080, 1993.
70. Wilker, E., Kiguchi, K., Bol, D., and DiGiovanni, J. Transgenic mice overexpressing IGF-1 in epidermis exhibit exaggerated sensitivity to diverse skin tumor promoting agents. Proc. Am. Assoc. Cancer Res., 39: 78-79, 1998.
71. Robertson, F. M., Ross, M. S., Tober, K. L., Long, B. W., and Oberyszyn, T. M. Inhibition of pro-inflammatory cytokine gene expression and papilloma growth during murine multistage carcinogenesis by pentoxifylline. Carcinogenesis (Lond.), 17: 1719-1728, 1996.
72. Ahmad, N., Gali, H., Javed, S., and Agarwal, R. Skin cancer chemopreventive effects of a flavonoid antioxidant silymarin are mediated via impairment of receptor tyrosine kinase signaling and perturbation in cell cycle progression. Biochem. Biophys. Res. Commun., 247: 294-301, 1998.
73. Berton, T. R., Conti, C. J., Rodriguez-Puebla, M., Locniskar, M. F., and Fischer, S. M. Cell cycle regulation by ultraviolet light in SKH-1 mouse epidermis. Proc. Am. Assoc. Cancer Res., 38: 3315, 1997.
74. Rodriguez-Puebla, M. L., Robles, A. I., Johnson, D. G., LaCava, M., and Conti, C. J. Synchronized proliferation induced by 12-O-tetradecanoylphorbol-13-acetate treatment of mouse skin: an in vivo model for cell cycle regulation. Cell Growth Differ., 9: 31-39, 1998.