Details

Autor(en) / Beteiligte

• Ma, Li-sha
• Jiang, Chang-you
• Cui, Min
• Lu, Rong
• Liu, Shan-shan
• Zheng, Bei-bei
• Li, Lin
• Li, Xia

Titel

Fluopsin C induces oncosis of human breast adenocarcinoma cells

Ist Teil von

• Acta pharmacologica Sinica, 2013-08, Vol.34 (8), p.1093-1100

Ort / Verlag

United States: Nature Publishing Group

Erscheinungsjahr

2013

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Aim： Fluopsin C, an antibiotic isolated from Pseudomonasjinanesis, has shown antitumor effects on several cancer cell lines. In the current study, the oncotic cell death induced by fluopsin C was investigated in human breast adenocarcinoma cells in vitro. Methods： Human breast adenocarcinoma cell lines MCF-7 and MD-MBA-231 were used. The cytotoxicity was evaluated using MTT assay. Time-lapse microscopy and transmission electron microscopy were used to observe the morphological changes. Cell membrane integrity was assessed with propidium iodide （PI） uptake and lactate dehydrogenase （LDH） assay. Flow cytometry was used to measure reactive oxygen species （ROS） level and mitochondrial membrane potential （hqJm）. A multimode microplate reader was used to analyze the intracellular ATP level. The changes in cytoskeletal system were investigated with Western blotting and immunostainin~ Results： Fluopsin C （0.5-8 pmol/L） reduced the cell viability in dose- and time-dependent manners. Its ICso values in MCF-7 and MD-MBA-231 cells at 24 h were 0.9 and 1.03 pmol/L, respectively. Fluopsin C （2 pmol/L） induced oncosis in both the breast adenocarcinoma cells characterized by membrane blebbing and swelling, which was blocked by pretreatment with the pan-caspase inhibitor Z-VAD-fmk. In MCF-7 cells, fluopsin C caused PI uptake into the cells, significantly increased LDH release, induced cytoskeleta system degradation and ROS accumulation, decreased the intracellular ATP level and △ψum. Noticeably, fluopsin C exerted comparable cytotoxicity against the normal human hepatocytes （HL7702） and human mammary epithelial cells with the IC5o values at 24 h of 2.7 and 2.4 pmol/L, respectively. Conclusion： Oncotic cell death was involved in the anticancer effects of fluopsin C on human breast adenocarcinoma cells in vitro. The hepatoxicity of fluopsin C should not be ignored.