A Sterol from Soft Coral Induces Apoptosis and Autophagy in MCF-7 Breast Cancer Cells
AbstractThe 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, these findings suggest the translational potential of compound 1 in breast cancer therapy. View Full-Text
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Weng, J.-R.; Chiu, C.-F.; Hu, J.-L.; Feng, C.-H.; Huang, C.-Y.; Bai, L.-Y.; Sheu, J.-H. A Sterol from Soft Coral Induces Apoptosis and Autophagy in MCF-7 Breast Cancer Cells. Mar. Drugs 2018, 16, 238.
Weng J-R, Chiu C-F, Hu J-L, Feng C-H, Huang C-Y, Bai L-Y, Sheu J-H. A Sterol from Soft Coral Induces Apoptosis and Autophagy in MCF-7 Breast Cancer Cells. Marine Drugs. 2018; 16(7):238.Chicago/Turabian Style
Weng, Jing-Ru; Chiu, Chang-Fang; Hu, Jing-Lan; Feng, Chia-Hsien; Huang, Chiung-Yao; Bai, Li-Yuan; Sheu, Jyh-Horng. 2018. "A Sterol from Soft Coral Induces Apoptosis and Autophagy in MCF-7 Breast Cancer Cells." Mar. Drugs 16, no. 7: 238.
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