A Sterol from Soft Coral Induces Apoptosis and Autophagy in MCF-7 Breast Cancer Cells

Marine Drugs
Jing-Ru WengJyh-Horng Sheu

Abstract

The peroxisome proliferator-activated receptor γ (PPARγ) is a nuclear receptor that plays a key role in regulating cellular metabolism, and is a therapeutic target for cancer therapy. To search for potential PPARγ activators, a compound library comprising 11 marine compounds was examined. Among them, a sterol, 3β,11-dihydroxy-9,11-secogorgost-5-en-9-one (compound 1), showed the highest PPARγ activity with an IC50 value of 8.3 μM for inhibiting human breast adenocarcinoma cell (MCF-7) growth. Western blotting experiments showed that compound 1 induces caspase activation and PARP cleavage. In addition, compound 1 modulated the expression of various PPARγ-regulated downstream biomarkers including cyclin D1, cyclin-dependent kinase (CDK)6, B-cell lymphoma 2 (Bcl-2), p38, and extracellular-signal-regulated kinase (ERK). Moreover, compound 1 increased reactive oxygen species (ROS) generation, upregulated the phosphorylation and expression of H2AX, and induced autophagy. Interestingly, pre-treatment with the autophagy inhibitor 3-methyladenine rescued cells from compound 1-induced growth inhibition, which indicates that the cytotoxic effect of compound 1 is, in part, attributable to its ability to induce autophagy. In conclusion, thes...Continue Reading

References

Jan 12, 2001·Molecular Cell Biology Research Communications : MCBRC·M FacompréC Bailly
Oct 28, 2003·Natural Product Research·Pei-Wen HsiehYang-Chang Wu
Aug 12, 2005·Organic Letters·Yen-Ju TsengJyh-Horng Sheu
Jun 4, 2008·Annual Review of Biochemistry·Peter Tontonoz, Bruce M Spiegelman
Sep 16, 2008·Cancer Letters·Shuo WeiChing-Shih Chen
Nov 14, 2008·Nature Reviews. Cancer·William M BonnerYves Pommier
Jan 12, 2010·Mutation Research·Olga A SedelnikovaWilliam M Bonner
Sep 3, 2010·Nature Reviews. Drug Discovery·Dan Jones
Oct 29, 2010·European Journal of Medicinal Chemistry·Zhi-Hong WenJyh-Horng Sheu
Apr 29, 2011·Cancer Biology & Therapy·Tunde O Akinyeke, LaMonica V Stewart
Oct 12, 2012·Annals of the New York Academy of Sciences·Ivana Vucenik, Joseph P Stains
Jun 19, 2013·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Wen-Li HsuWei-Chiao Chang
Jul 9, 2013·Seminars in Cancer Biology·He LiuHans-Uwe Simon
Dec 3, 2013·Molecular Carcinogenesis·Christelle Colin-CassinIsabelle Grillier-Vuissoz
May 2, 2014·Journal of Cellular and Molecular Medicine·Feng ZhangShizhong Zheng
Aug 2, 2014·Biochemical Pharmacology·Limei WangAtanas G Atanasov
Feb 9, 2016·Journal of Natural Products·David J Newman, Gordon M Cragg
Mar 2, 2016·Scientific Reports·Li-Yuan BaiJing-Ru Weng
May 3, 2016·Journal of Receptor and Signal Transduction Research·Fengyun WangZhenyu Bi
Jun 4, 2016·Bioorganic & Medicinal Chemistry Letters·Wan-Ru TsengJyh-Horng Sheu
Jun 5, 2016·The Journal of Nutritional Biochemistry·Cheng-Hung ChuangYing-Hsuna Wang
Aug 16, 2016·Apoptosis : an International Journal on Programmed Cell Death·Hai-Bin ZhangZhao-Jun Wang
Oct 30, 2016·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Yoon-Jin LeeSang-Han Lee
Sep 17, 2016·International Journal of Oncology·Shinji MikamiTadashi Kitahara
Jun 8, 2017·Seminars in Cell & Developmental Biology·Jennifer N Moloney, Thomas G Cotter
Jun 26, 2017·Chinese Journal of Cancer·Ying-Jie LiZhe-Sheng Chen

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Citations

Feb 7, 2020·Natural Product Reports·Anthony R CarrollMichèle R Prinsep
Jul 4, 2019·International Journal of Molecular Sciences·Fu Ou-YangHsueh-Wei Chang
Sep 25, 2020·Marine Drugs·Sergey A Dyshlovoy
Dec 6, 2020·Marine Drugs·Ekaterina V ErmolenkoValery M Dembitsky
Apr 6, 2021·World Journal of Biological Chemistry·Rama Rao MallaGanji Purnachandra Nagaraju
Jul 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Sheng-Chieh WangHsueh-Wei Chang

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Methods Mentioned

BETA
flow cytometry

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