Fengycin inhibits the growth of the human lung cancer cell line 95D through reactive oxygen species production and mitochondria-dependent apoptosis.

Abstract

To investigate the antitumor activity and action mechanism of fengycin using the human lung cancer cell line 95D. The antitumor activity of fengycin was tested in vitro and in vivo. Reactive oxygen species production, Ca(2+) uptake, and mitochondrial membrane potential loss induced by fengycin in 95D cells were measured by flow cytometry and a laser confocal microscope. Lactate dehydrogenase release and caspase activity in fengycin-treated 95D cells were assayed using cytotoxicity detection kits. Apoptosis triggered by fengycin was identified by 4,6-diamidino-2-phenylindole (DAPI) staining and flow cytometry. The effects of fengycin on cell-cycle and apoptosis-related proteins were evaluated by quantitative reverse-transcription PCR and western blot. Treatment with fengycin not only significantly decreased cell proliferation in various cancer cell lines including 95D but inhibited the growth of xenografted 95D cells in nude mice. Fengycin also induced reactive oxygen species production and Ca(2+) uptake, as well as lactate dehydrogenase release and mitochondrial membrane potential loss. Further experiments showed that fengycin could trigger apoptosis in 95D cells and cause cell-cycle arrest at the G0/G1 stage by downregulating cyclin D1 and cyclin-dependent kinase 4 (CDK4). While investigating caspase activity and the expression of apoptosis-related proteins, fengycin was found to induce apoptosis in 95D cells through the mitochondrial pathway, evidenced by increased caspase activity, Bax expression, and cytochrome c release into the cytoplasm, as well as decreased Bcl-2 levels. Fengycin can inhibit the growth of the cancer cell line 95D by regulating the cell cycle and promoting apoptosis, suggesting that it may have potential as an anticancer treatment.

• Authors: Hongping Yin, Chuanlong Guo, Ying Wang, Dan Liu, Yunbin Lv, Fengxia Lv, Zhaoxin Lu
• Journal: Anti-cancer drugs (Anticancer Drugs) Vol. 24 Issue 6 Pg. 587-98 (Jul 2013) ISSN: 1473-5741 [Electronic] England
• PMID: 23552471 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Lipopeptides
• Reactive Oxygen Species
• fengycin
• Cyclin D1
• L-Lactate Dehydrogenase
• Cyclin-Dependent Kinase 4
• Caspases
• Calcium

Topics

• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Calcium (metabolism)
• Caspases (metabolism)
• Cell Cycle (drug effects)
• Cell Line, Tumor
• Cyclin D1 (metabolism)
• Cyclin-Dependent Kinase 4 (metabolism)
• Flow Cytometry
• Gene Expression Regulation, Neoplastic (drug effects)
• Genes, Neoplasm (drug effects)
• Humans
• L-Lactate Dehydrogenase (biosynthesis)
• Lipopeptides (pharmacology)
• Lung Neoplasms (drug therapy)
• Microscopy, Confocal
• Mitochondrial Membranes (metabolism)
• Reactive Oxygen Species (metabolism)