Cutaneous melanoma is one of the most aggressive forms of skin cancer. Arctigenin, one of the major bioactive compo-nents of Arctii Fructus, has been reported to exhibit antioxidant, antitumor and anti-inflammatory activities. In the pre-sent study, we investigated the effect of arctigenin on induction of apoptosis in highly metastatic SK-MEL-28 human melanoma cells. Arctigenin inhibited growth of SK-MEL-28 cells in a dose-dependent manner. Treatment of SK-MEL-28cells with arctigenin caused cleavage of caspases 3, 7 and 9, and poly (ADP-ribose) polymerase in a dose-dependent manner. Furthermore, acetylation of histone H3 and H4 in the SK-MEL-28 cells was dramatically increased by arctigenin treatment. Collectively, these findings indicate that arctigenin-induces apoptosis of SK-MEL-28 melanoma cells via activation of caspases and histone acetylation.
C. R. Wolf, “Chemoprevention: Increased Potential to Bear Fruit,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 98, No. 6, 2001, pp. 2941-2943. doi:10.1073/pnas.071042698
C. S. Yang, J. M. Landau, M. T. Huang and H. L. Newmark, “Inhibition of Carcinogenesis by Dietary Polyphenolic Compounds,” Annual Review of Nutrition, Vol. 21, 2001, pp. 381-406. doi:10.1146/annurev.nutr.21.1.381
M. Nihal, N. Ahmad, H. Mukhtar and G. S. Wood, “Anti-proliferative and Proapoptotic Effects of epigallo- catechin-3-gallate on Human Melanoma: Possible Implications for the Chemoprevention of Melanoma,” International Journal of Cancer, Vol. 114, No. 4, 2005, pp. 513-521. doi:10.1002/ijc.20785
S. Caltagirone, C. Rossi, A. Poggi, F. O. Ranelletti, P. G. Natali, M. Brunetti, F. B. Aiello and M. Piantelli, “Flavonoids Apigenin and Quercetin Inhibit Melanoma Growth and Metastatic Potential,” International Journal of Cancer, Vol. 87, No. 4, 2000, pp. 595-600.
J. A. Milner, S. S. McDonald, D. E. Anderson and P. Greenwald, “Molecular Targets for Nutrients Involved with Cancer Prevention,” Nutrition and Cancer, Vol. 41, No. 1-2, 2001, pp. 1-16.
S. Awale, J. Lu, S. K. Kalauni, Y. Kurashima, Y. Tezuka, S. Kadota and H. Esumi, “Identification of Arctigenin as an Antitumor Agent having the Ability to Eliminate the Tolerance of Cancer Cells to Nutrient Starvation,” Cancer Research, Vol. 66, No. 3, 2006, pp. 1751-1757.
M. K. Cho, Y. P. Jang, Y. C. Kim and S. G. Kim, “Arctigenin, a Phenylpropanoid Dibenzylbutyrolactone Lignan, Inhibits MAP Kinases and AP-1 Activation via Potent MKK Inhibition: The Role in TNF-α Inhibition,” International Immunopharmacology, Vol. 4, No. 10-11, 2004, pp. 1419-1429. doi:10.1016/j.intimp.2004.06.011
T. Matsumoto, K. Hosono-Nishiyama and H. Yamada, “Anti-proliferative and Apoptotic Effects of Butyrolactone Lignans from Arctium Lappa on Leukemic Cells,” Planta Medica, Vol. 72, No. 3, 2006, pp. 276-278.
Y. P. Jang, S. R. Kim, Y. H. Choi, J. Kim, S. G. Kim and G. J. Markelonis, T. H. Oh and Y. C. Kim, “Arctigenin Protects Cultured Cortical Neurons from Glutamate-Induced Neurodegeneration by Binding to Kainate Receptor,” Journal of Neuroscience Research, Vol. 68, No. 2, 2002, pp. 233-240. doi:10.1002/jnr.10204
K. Umehara, M. Nakamura, T. Miyase, M. Kuroyanagi and A. Ueno, “Studies on Differentiation Inducers: VI. Lignan Derivatives from Arctium Fructus (2),” Chemical & Pharmaceutical Bulletin, Vol. 44, No. 12, 1996, pp. 2300-2304.
T. M. Pawlik and V. K. Sondak, “Malignant Melanoma: Current State of Primary and Adjuvant Treatment,” Critical Reviews in Oncology/Hematology, Vol. 45, No. 3, 2003, pp. 245-264. doi:10.1016/S1040-8428(02)00080-X
P. Hersey, “Apoptosis and Melanoma: How New Insights are Effecting the Development of New Therapies for Melanoma,” Current Opinion in Oncology, Vol. 18, No. 2, 2006, pp. 189-196.
A. W. Throne, D. Kmiciek, P. Sautiere and C. Crane-Robinson, “Patterns of Histone Acetylation,” European Journal of Biochemistry, Vol. 193, No. 3, 1990, pp. 701-713. doi:10.1111/j.1432-1033.1990.tb19390.x
D. G. Edmondson, J. K. Davie, J. Zhou, B. Mirnikjoo, K. Tatchell and S. Y. R. Dent, “Site-specific Loss of Acetylation upon Phosphorylation of Histone H3,” Journal of Biological Chemistry, Vol. 277, No. 33, 2002, pp. 29496-29502. doi:10.1074/jbc.M200651200
N. Druesne, A. Pagniez, C. Mayeur, M. Thomas, C. Cherbuy, P. H. Duee, P. Martel and C. Chaumontet, “Diallyl Disulfide (DADS) Increases Histone Acetylation and p21(waf1/cip1) Expression in Human Colon Tumor Cell Lines,” Carcinogenesis, Vol. 25, No. 7, 2004, pp. 1227-1236.
R. J. Bold, S. Virudachalam and D. J. McConkey, “BCL2 Expression Correlates with Metastatic Potential in Pancreatic Cancer Cell Lines,” Cancer, Vol. 92, No. 5, 2001, pp. 1122-1129. doi:10.1002/1097-0142(20010901)92:5< 1122::AID-CNCR1429>3.0.CO;2-H
H. S. Jun, T. Park, C. K. Lee, M. K. Kang, M. S. Park, H. I. Kang, Y. J. Surh and O. H. Kim, “Capsaicin Induced Apoptosis of B16-F10 Melanoma Cells through Down- regulation of Bcl-2,” Food and Chemical Toxicology, Vol. 45, No. 5, 2007, pp. 708-715.
M. Mouria, A. S. Gukovskay, Y. Jung, P. Buechler, O. J. Hines, H. A. Reber and S. J. Pandol, “Food-derived Polyphenols Inhibit Pancreatic Cancer Growth through Mitochondrial Cytochrome c Release and Apoptosis,” International Journal of Cancer, Vol. 98, No. 5, 2002, pp. 761-769.