Fumigaclavine C from a marine-derived fungus Aspergillus fumigatus induces apoptosis in MCF-7 breast cancer cells.

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.

• Authors: Yong-Xin Li, S W A Himaya, Pradeep Dewapriya, Chen Zhang, Se-Kwon Kim
• Journal: Marine drugs (Mar Drugs) Vol. 11 Issue 12 Pg. 5063-86 (Dec 13 2013) ISSN: 1660-3397 [Electronic] Switzerland
• PMID: 24351905 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Ergot Alkaloids
• Indole Alkaloids
• NF-kappa B
• fumigaclavine C
• Mitogen-Activated Protein Kinases
• Matrix Metalloproteinase 2
• Matrix Metalloproteinase 9

Topics

• Apoptosis (drug effects, genetics)
• Aspergillus fumigatus (metabolism)
• Breast Neoplasms (drug therapy, genetics, metabolism)
• Cell Cycle (drug effects, genetics)
• Cell Line, Tumor
• Cell Movement (drug effects, genetics)
• Cell Proliferation (drug effects)
• Cell Survival (drug effects, genetics)
• DNA Fragmentation (drug effects)
• Down-Regulation (drug effects, genetics)
• Ergot Alkaloids (pharmacology)
• Female
• Humans
• Indole Alkaloids (pharmacology)
• MCF-7 Cells
• Matrix Metalloproteinase 2 (genetics, metabolism)
• Matrix Metalloproteinase 9 (genetics, metabolism)
• Mitogen-Activated Protein Kinases (genetics, metabolism)
• NF-kappa B (genetics, metabolism)
• Signal Transduction (drug effects, genetics)