期刊
ONCOLOGY LETTERS
卷 13, 期 5, 页码 3760-3766出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/ol.2017.5945
关键词
choroidal melanoma; cepharanthine; apoptosis; reactive oxygen species; c-Jun N-terminal kinase
类别
资金
- National Natural Science Foundation of China [81201188, 81472344]
- International Cooperation Project of Jilin Provincial Science and Technology Department [20150414031GH]
Choroidal melanoma is the most common primary intraocular tumor in adults. Cepharanthine (CEP), a natural alkaloid extracted from the roots of Stephania cepharantha Hayata, has been demonstrated to inhibit the proliferation of various cancer cells. However, its potential anticancer effect in choroidal melanoma has not been clarified yet. In the present study, it was identified that CEP may potently inhibit the proliferation of human choroidal melanoma cells, induce cell death and cell cycle arrest, and activate cellular apoptotic proteins, including Bcl-2-associated X protein, caspase and poly(ADP-ribose) polymerase. Results also revealed that CEP induced the cellular production of reactive oxygen species (ROS) and led to cytochrome c release, whereas concurrent treatment with N-acetyl-L-cysteine (a ROS scavenger) attenuated the situation. In addition, CEP was also revealed to activate c-Jun N-terminal kinase (JNK) and 2, whereas inhibition of JNK1/2 partially abrogated the proliferation inhibitory effect of CEP, indicating that JNK1/2 and JNK2 were involved in CEP-triggered cellular apoptosis. In addition, the anticancer effects of CEP were also observed in a choroidal melanoma xenograft model. In summary, the results of the present study demonstrated that CEP is effective in suppressing human choroidal melanoma cell and tumor cell proliferation, and that CEP may therefore represent a potentially novel therapeutic agent for the treatment of choroidal melanoma.
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