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Heteronemin, a Spongean Sesterterpene, Induces Cell Apoptosis and Autophagy in Human Renal Carcinoma Cells
Joint Authors
Wu, Szu-Ying
Sung, Ping-Jyun
Chang, Ya-Ling
Pan, Shiow-Lin
Teng, Che-Ming
Source
Issue
Vol. 2015, Issue 2015 (31 Dec. 2015), pp.1-13, 13 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2015-05-18
Country of Publication
Egypt
No. of Pages
13
Main Subjects
Abstract EN
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 IC50 value of 1.57 μM by MTT assay and a GI50 value of 0.77 μM 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.
American Psychological Association (APA)
Wu, Szu-Ying& Sung, Ping-Jyun& Chang, Ya-Ling& Pan, Shiow-Lin& Teng, Che-Ming. 2015. Heteronemin, a Spongean Sesterterpene, Induces Cell Apoptosis and Autophagy in Human Renal Carcinoma Cells. BioMed Research International،Vol. 2015, no. 2015, pp.1-13.
https://search.emarefa.net/detail/BIM-1056572
Modern Language Association (MLA)
Wu, Szu-Ying…[et al.]. Heteronemin, a Spongean Sesterterpene, Induces Cell Apoptosis and Autophagy in Human Renal Carcinoma Cells. BioMed Research International No. 2015 (2015), pp.1-13.
https://search.emarefa.net/detail/BIM-1056572
American Medical Association (AMA)
Wu, Szu-Ying& Sung, Ping-Jyun& Chang, Ya-Ling& Pan, Shiow-Lin& Teng, Che-Ming. Heteronemin, a Spongean Sesterterpene, Induces Cell Apoptosis and Autophagy in Human Renal Carcinoma Cells. BioMed Research International. 2015. Vol. 2015, no. 2015, pp.1-13.
https://search.emarefa.net/detail/BIM-1056572
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1056572