Alternol exerts prostate-selective antitumor effects through modulations of the AMPK signaling pathway.

Abstract

BACKGROUND:

Alternol is an original compound purified from the fermentation products of Alternaria alternata var. monosporus, a microorganism from the bark of the yew tree. It has been reported that Alternol can inhibit proliferation of mouse leukemia cells and human gastric carcinoma cells, the aim of this study was to investigate the effects of Alternol on prostate cancer cells in comparison to prostate cells.

METHODS:

The MTT assay was utilized to assess cell viability. Cell cycle was analyzed by flow cytometry with propidium iodide staining. Protein expression levels were examined by Western blotting.

RESULTS:

Alternol treatment resulted in a significant decrease in the viability of prostate cancer cells but had lesser effects on prostate cells. Alternol inhibited AMP-activated protein kinase (AMPK) phosphorylation in prostate cancer C4-2 cells but stimulated AMPK phosphorylation in prostate RWPE-1 cells. Inhibition of p27 phosphorylation was observed in C4-2 cells whereas a promotion of p27 phosphorylation was seen in RWPE-1 cells. Alternol treatment resulted in a profound increase in the LC3II/LC3I protein ratio in RWPE-1 cells but not in C4-2 cells. A dose-dependent down-regulation of Bcl-2 protein was detected in C4-2 cells but not in RWPE-1 cells. Pretreatment of cells with Compound C (AMPK inhibitor) before Alternol treatment abolished the selective antitumor effect of Alternol.

CONCLUSIONS:

These results reveal for the first time that Alternol exerts a selective antitumor effect on prostate cancer cells when compared with RWPE-1 prostate epithelial cells. In addition, the AMPK signaling pathway is responsible for the selective antitumor effects of Alternol.

• Authors: Eddie D Yeung, Alex Morrison, Daniel Plumeri, Jingying Wang, Chao Tong, Xiaoyan Yan, Ji Li
• Journal: The Prostate (Prostate) Vol. 72 Issue 2 Pg. 165-72 (Feb 01 2012) ISSN: 1097-0045 [Electronic] United States
• PMID: 21538425 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Wiley Periodicals, Inc.

Chemical References

• Alternol
• Formazans
• Heterocyclic Compounds, 4 or More Rings
• Proto-Oncogene Proteins c-bcl-2
• Pyrazoles
• Pyrimidines
• Tetrazolium Salts
• dorsomorphin
• Cyclin-Dependent Kinase Inhibitor p27
• MTT formazan
• AMP-Activated Protein Kinases

Topics

• AMP-Activated Protein Kinases (antagonists & inhibitors, metabolism)
• Autophagy (drug effects)
• Blotting, Western
• Cell Cycle (drug effects)
• Cell Line
• Cell Line, Tumor
• Cell Survival (drug effects)
• Cyclin-Dependent Kinase Inhibitor p27 (metabolism)
• Drug Interactions
• Flow Cytometry
• Formazans (chemistry)
• Heterocyclic Compounds, 4 or More Rings (pharmacology)
• Humans
• Male
• Phosphorylation (drug effects)
• Prostate (drug effects)
• Prostatic Neoplasms (drug therapy, enzymology, metabolism, pathology)
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Pyrazoles (pharmacology)
• Pyrimidines (pharmacology)
• Signal Transduction (drug effects)
• Tetrazolium Salts (chemistry)