Heteronemin, a spongean sesterterpene, induces cell apoptosis and autophagy in human renal carcinoma cells

Szu Ying Wu, Ping Jyun Sung, Ya Ling Chang, Shiow Lin Pan, Che Ming Teng

研究成果: 雜誌貢獻文章同行評審

26 引文 斯高帕斯(Scopus)

摘要

Heteronemin is a bioactive marine sesterterpene isolated from the sponge Hyrtios sp. Previous reports have shown that heteronemin possesses anticancer activity. Here, heteronemin displayed cytotoxic effects against three human cancer cell lines (A549, ACHN, and A498) and exhibited potent activity in A498 human renal carcinoma cells, with an ICvalue of 1.57 M by MTT assay and a GIvalue of 0.77 M by SRB assay. Heteronemin initiates apoptotic cell death by downregulating Bcl-2 and Bcl-xL and upregulating Bax, leading to the disruption of the mitochondrial membrane potential and the release of cytochrome c from the mitochondria. These effects were associated with the activation of caspase-3/caspase-8/caspase-9, followed by PARP cleavage. Furthermore, heteronemin inhibited the phosphorylation of AKT signaling pathway and ERK and activated p38 and JNK. The specific inhibition of the p38 pathway by SB203580 or p38 siRNA treatment reversed the heteronemin-induced cytotoxicity and apoptotic signaling. Heteronemin also induced autophagy in A498 cells, and treatment with chloroquine (autophagy inhibitor) or SP600125 (JNK inhibitor) inhibited autophagy and increased heteronemin-induced cytotoxicity and apoptotic signaling. Taken together, this study proposes a novel treatment paradigm in which the combination of heteronemin and autophagy inhibitors leads to enhanced RCC cell apoptosis.
原文英語
文章編號738241
期刊BioMed Research International
2015
DOIs
出版狀態已發佈 - 2015

ASJC Scopus subject areas

  • 免疫學與微生物學 (全部)
  • 生物化學、遺傳與分子生物學 (全部)

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