Cepharanthine exerts antitumor activity on choroidal melanoma by reactive oxygen species production and c-Jun N-terminal kinase activation

Zhu,Qi; Guo,Baofeng; Chen,Linlin; Ji,Qiuye; Liang,Hang; Wen,Naiyan; Zhang,Ling

doi:10.3892/ol.2017.5945

Cepharanthine exerts antitumor activity on choroidal melanoma by reactive oxygen species production and c-Jun N-terminal kinase activation

Authors:
- Qi Zhu
- Baofeng Guo
- Linlin Chen
- Qiuye Ji
- Hang Liang
- Naiyan Wen
- Ling Zhang
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Affiliations: Department of Pathophysiology, College of Basic Medicine Sciences, Jilin University, Changchun, Jilin 130021, P.R. China, Department of Plastic Surgery, The China‑Japan Union Hospital, Jilin University, Changchun, Jilin 130021, P.R. China, Department of Ophthalmology, The Fourth Hospital of Shenyang, Shenyang, Liaoning 110031, P.R. China
Published online on: March 29, 2017 https://doi.org/10.3892/ol.2017.5945
Pages: 3760-3766

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Abstract

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) 1 and 2, whereas inhibition of JNK1/2 partially abrogated the proliferation inhibitory effect of CEP, indicating that JNK1 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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