Bufotalin induces cell cycle arrest and cell apoptosis in human malignant melanoma A375 cells

Pan,Zhaohai; Qu,Chuanjun; Chen,Ying; Chen,Xiaoyu; Liu,Xiaona; Hao,Wenjin; Xu,Wenjuan; Ye,Lei; Lu,Peng; Li,Defang; Zheng,Qiusheng

doi:10.3892/or.2019.7032

Bufotalin induces cell cycle arrest and cell apoptosis in human malignant melanoma A375 cells

Authors:
- Zhaohai Pan
- Chuanjun Qu
- Ying Chen
- Xiaoyu Chen
- Xiaona Liu
- Wenjin Hao
- Wenjuan Xu
- Lei Ye
- Peng Lu
- Defang Li
- Qiusheng Zheng
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Affiliations: School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University, Yantai, Shandong 264003, P.R. China, Department of Education, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong 264003, P.R. China
Published online on: February 26, 2019 https://doi.org/10.3892/or.2019.7032
Pages: 2409-2417

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Abstract

Venenum bufonis has been used as an antitumor drug in China for many years. Bufotalin, as an active component of Venenum bufonis, has been proven to exhibit antitumor effects in cancer types. In the present study, the effect of bufotalin on the human melanoma skin cancer cell line A375 was analyzed using MTT and colony formation assays. Bufotalin significantly inhibited the proliferation and colony formation of A375 cells. Further studies demonstrated that bufotalin significantly upregulated the protein levels of ATM serine/threonine kinase and Chk2, downregulated CDC25C protein expression, and subsequently inhibited CDK1 expression, leading to cell cycle arrest at the G2/M phase of the A375 cells. Furthermore, bufotalin significantly increased BAX expression levels, decreased BCL‑2 expression, and then upregulated apoptosis‑related proteins, caspase‑3/-9, followed by A375 cell apoptosis. Taken together, these results show that bufotalin induces cell cycle arrest at the G2/M phase and cell apoptosis, resulting in the inhibition of A375 cell proliferation, thereby suggesting that bufotalin may be utilized in melanoma treatment.

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