|Title:||Heteronemin, a spongean sesterterpene, induces cell apoptosis and autophagy in human renal carcinoma cells||Authors:||CHE-MING TENG||Issue Date:||2015||Journal Volume:||2015||Source:||BioMed Research International||Abstract:||
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. ? 2015 Szu-Ying Wu et al.
|DOI:||10.1155/2015/738241||SDG/Keyword:||anthra[1,9 cd]pyrazol 6(2h) one; caspase 3; caspase 8; caspase 9; chloroquine; cytochrome c; heteronemin; mitogen activated protein kinase p38; protein Bax; protein bcl 2; protein bcl xl; sesterterpene; small interfering RNA; stress activated protein kinase; unclassified drug; heteronemin; terpene; tumor protein; antineoplastic activity; apoptosis; Article; autophagy; cancer cell line; carcinoma cell; controlled study; drug potency; human; human cell; IC50; kidney carcinoma; mitochondrial membrane potential; MTT assay; sponge (Porifera); apoptosis; autophagy; biosynthesis; Carcinoma, Renal Cell; cell proliferation; drug effects; gene expression regulation; genetics; pathology; tumor cell line; Hyrtios; Apoptosis; Autophagy; Carcinoma, Renal Cell; Cell Line, Tumor; Cell Proliferation; Gene Expression Regulation, Neoplastic; Humans; Neoplasm Proteins; Terpenes
|Appears in Collections:||醫學系|
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