Inhibitory effect of melatonin on the growth of H22 hepatocarcinoma cells by inducing apoptosis

Abstract

Whether melatonin not only inhibits the growth of H22 hepatocarcinoma cells but also induces apoptosis in vitro was assessed. The anti-proliferative effects of melatonin on tumor cells was observed by MTT assay and tumor cells growth curve assay. And the apoptosis of the cells was studied by acridine orange fluorescence assay and flow cytometry. The cell cycle of the tumor cells was also observed by flow cytometry. It was found that melatonin could significantly inhibit the growth of H22 hepatocarcinoma cells. Incubated with melatonin, chromatin condensation of the tumor cells was observed by fluorescence microscopy. Compared with control, the percentage of appoptotic cells was increased, and the proportion of G₀/S increased but that of G₂/M decreased. It was suggested that melationin could directly inhibit the growth of H22 hepatocarcinoma cells by inducing apoptosis and extending the length of cell cycle of the tumor cells.

Keywords

melatonin / hepatocarcinoma / apoptosis / cell cycle

References

[1] BlaskD E, SauerL A, DauchyR T. Melatonin as a chronobiotic/anticancer agent: cellular, biochemical, and molecular mechanism of action and their implication for circadian-based cancer therapy. Curr Top Med Chem, 2002, 2(2): 113-113

[2] LissoniP. Modulation of anticancer cytokines IL-2 and IL-12 by melatonin and other pineal indoles 5-methoxytryptamine and 5-methoxytraptophol in treatment of human neoplasms. Ann N Y Acad Sci., 2000, 917: 560-560

[3] ReiterR J, TanD X, CabreraJ, et al.. The oxidant/antioxidant network: role of melatonin. Bio Signals Recept, 1999, 8(1–2): 56-56

[4] MediavillaM D, CosS, SanchezE J. Melatonin inereases P53 and P21 WAF1 expression in MCF-7 human breast cancer cells in vitro. Life Sci, 1999, 65(4): 415-415

[5] QinL, WangX M, ChenJ, et al.. Assessment of ability of melatonin to regulate cytokine production by perito neal macrophages. Tumor(Chinese), 2003, 23(2): 119-119

[6] ShuiS Y W, XiS C, XuJ N, et al.. Inhibition of malignant trophoblastic cell proliferation in vitro and in vivo by melatonin. Life Sci, 2000, 67: 2059-2059

[7] GaoL, XuR K, HeS F, et al.. Inhibitory effects of melatonin on the development of 17-beta-estradiol induced prolactinoma. Zhongguo Yi Xue Ke Xue Yuan Xue Bao (Chinese), 2001, 23(1): 49-51

[8] Acuna-CostroviejoD, ReiterR J, Menedez-PelaezA, et al.. Characterization of high-affinity melatonin binding sites in purified cell nuclei of rat liver. J Pineal Res, 1994, 16(2): 100-100

[9] YanJ J, ShenF, WuMC. Immunoregulation and antitumor effect of melatonin on H22 hepatocarcinoma mouse. Di Er Jun Yi Da Xue Xue Bao(Chinese), 2004, 17(5): 427-427

[10] MarelliM M, LimontaP, MaggiR, et al.. Growth-inhibitory activity of melatonin on human androgen-independent DU145 prostate cancer cells. Prostate, 2000, 45(3): 238-238

[11] CosS, RecioJ, SanchezE J. Modulation of the cell cycle time of MCF-7 human breast cancer cells by melatonin. Life Sci, 2004, 58(9): 811-811