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Fumigaclavine C from a Marine-Derived Fungus Aspergillus Fumigatus Induces Apoptosis in MCF-7 Breast Cancer Cells
Marine Bioprocess Research Center, Pukyong National University, Busan 608-737, Korea
Department of Chemistry, Pukyong National University, Busan 608-737, Korea
Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China
* Author to whom correspondence should be addressed.
Received: 1 October 2013; in revised form: 30 November 2013 / Accepted: 2 December 2013 / Published: 13 December 2013
Abstract: Recently, much attention has been given to discovering natural compounds as potent anti-cancer candidates. In the present study, the anti-cancer effects of fumigaclavine C, isolated from a marine-derived fungus, Aspergillus fumigatus, was evaluated in vitro. In order to investigate the impact of fumigaclavine C on inhibition of proliferation and induction of apoptosis in breast cancer, MCF-7 cells were treated with various concentrations of fumigaclavine C, and fumigaclavine C showed significant cytotoxicity towards MCF-7 cells. Anti-proliferation was analyzed via cell mobility and mitogen-activated protein kinase (MAPK) signaling pathway. In addition, fumigaclavine C showed potent inhibition on the protein and gene level expressions of MMP-2, -9 in MCF-7 cells which were manifested in Western blot and reverse transcription polymerase chain reaction (RT-PCR) results. The apoptosis induction abilities of the fumigaclvine C was studied by analyzing the expression of apoptosis related proteins, cell cycle analysis, DNA fragmentation and molecular docking studies. It was found that fumigaclavine C fragmented the MCF-7 cell DNA and arrested the cell cycle by modulating the apoptotic protein expressions. Moreover, fumigaclavine C significantly down-regulated the NF-kappa-B cell survival pathway. Collectively, data suggest that fumigaclavine C has a potential to be developed as a therapeutic candidate for breast cancer.
Keywords: fumigaclavine C; apoptosis; anti-proliferation; mitochondrial pathway; anti-cancer
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MDPI and ACS Style
Li, Y.-X.; Himaya, S.; Dewapriya, P.; Zhang, C.; Kim, S.-K. Fumigaclavine C from a Marine-Derived Fungus Aspergillus Fumigatus Induces Apoptosis in MCF-7 Breast Cancer Cells. Mar. Drugs 2013, 11, 5063-5086.
Li Y-X, Himaya S, Dewapriya P, Zhang C, Kim S-K. Fumigaclavine C from a Marine-Derived Fungus Aspergillus Fumigatus Induces Apoptosis in MCF-7 Breast Cancer Cells. Marine Drugs. 2013; 11(12):5063-5086.
Li, Yong-Xin; Himaya, S.W.A.; Dewapriya, Pradeep; Zhang, Chen; Kim, Se-Kwon. 2013. "Fumigaclavine C from a Marine-Derived Fungus Aspergillus Fumigatus Induces Apoptosis in MCF-7 Breast Cancer Cells." Mar. Drugs 11, no. 12: 5063-5086.