Tephrosin-induced autophagic cell death in A549 non-small cell lung cancer cells.

Abstract

Anticancer effect of tephrosin (1) has been documented; however, the molecular mechanisms underlying the cytotoxicity of tephrosin in cancer cells remain unclear. In the present paper, the proliferation inhibition rate of several cancer cells was tested using the MTT assay; cell cycle, reactive oxygen species (ROS), and mitochondrial membrane potential (MMP) were determined by flow cytometry; poly(ADP-ribose) polymerase (PARP) cleavage and heat shock protein 90 (Hsp90) expression were evaluated by Western blotting; autophagy was examined by confocal microscopy and light chain 3 (LC3) conversion assay. The results showed that exposure of the cells to tephrosin induced significant proliferation inhibition in a dose-dependent manner, especially on A549 with G(2)/M being arrested. Tephrosin was not found to induce cell apoptosis as PARP cleavage was not detected after 24 h treatment, but the formation of acidic vesicular organelle of autophagy character was found, and autophagy was further confirmed by the increase in the ratio of LC3-II to LC3-I. It was observed that tephrosin induced ROS generation and Hsp90 expression inhibition. These results indicate that tephrosin induces A549 cancer cell death via the autophagy pathway, and the roles of ROS generation and Hsp90 expression inhibition in this process need further study in the future.

• Authors: Jing Li, Xiao-Lu Wang, Yu-Chun Fang, Chang-Yun Wang
• Journal: Journal of Asian natural products research (J Asian Nat Prod Res) Vol. 12 Issue 11 Pg. 992-1000 (Nov 2010) ISSN: 1477-2213 [Electronic] England
• PMID: 21061222 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Phytogenic
• HSP90 Heat-Shock Proteins
• Reactive Oxygen Species
• Rotenone
• tephrosin
• Poly(ADP-ribose) Polymerases

Topics

• Antineoplastic Agents, Phytogenic (chemistry, pharmacology)
• Autophagy (drug effects)
• Carcinoma, Non-Small-Cell Lung
• Cell Cycle (drug effects)
• Dose-Response Relationship, Drug
• Drug Screening Assays, Antitumor
• HSP90 Heat-Shock Proteins (analysis)
• Humans
• Membrane Potential, Mitochondrial (drug effects)
• Microscopy, Confocal
• Molecular Structure
• Poly(ADP-ribose) Polymerases (metabolism)
• Reactive Oxygen Species (analysis)
• Rotenone (analogs & derivatives, chemistry, pharmacology)