Bafilomycin C1 induces G0/G1 cell-cycle arrest and mitochondrial-mediated apoptosis in human hepatocellular cancer SMMC7721 cells

The Journal of Antibiotics
Xiaoxiao GaoXueshi Huang

Abstract

Bafilomycin C1, which was isolated from Streptomyces albolongus in our previous work, exhibited strong cytotoxicity against several cancer cell lines. This study aimed to evaluate its antitumor effect on human hepatocellular cancer SMMC7721 cells and the underlying mechanism in vitro and in vivo. MTT assay revealed that bafilomycin C1 retarded SMMC7721 cell growth and proliferation. Western blot and real-time qPCR analysis revealed that bafilomycin C1 caused partial G0/G1 phase cell-cycle arrest, downregulated the expression of cyclin D3, cyclin E1, CDK2, CDK4, and CDK6 and upregulated the expression of p21. Moreover, bafilomycin C1 caused mitochondrial membrane dysfunction through oxidative stress. Furthermore, bafilomycin C1 decreased the expression of Bcl-2; increased the expression of Bax, p53, and P-p53; and increased cleavage of caspase-9 and caspase-3, thereby inducing the intrinsic caspase-dependent apoptotic pathway. In vivo experiments in mice suggested that bafilomycin C1 suppressed tumor growth with few side effects. Cell-cycle arrest and induced apoptosis in tumor tissues in a mouse model treated with bafilomycin C1 were demonstrated by histological analyses, western blot and TUNEL. These findings indicate that baf...Continue Reading

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Citations

Apr 23, 2019·Hepatology Research : the Official Journal of the Japan Society of Hepatology·Shen ShenZhenfeng Duan
Nov 21, 2019·International Journal of Molecular Medicine·Zhongrong GuoYuanliang Huang
Sep 10, 2020·Proceedings of the National Academy of Sciences of the United States of America·Mark M PainterKathleen L Collins
Jul 17, 2019·European Journal of Pharmacology·Marina StamenkovicVladimir Trajkovic
May 4, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Chunhui JiangLei Gu

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Methods Mentioned

BETA
xenograft
Assay
PCR
Protein Assay
flow cytometry
xenografts

Software Mentioned

SPSS

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