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Pterostilbene induces autophagy and apoptosis in sensitive and chemoresistant human bladder cancer cells.
- Source :
-
Molecular nutrition & food research [Mol Nutr Food Res] 2010 Dec; Vol. 54 (12), pp. 1819-32. - Publication Year :
- 2010
-
Abstract
- Scope: Bladder cancer is one of the most common malignancies in the world. The majority of bladder cancer deaths are due to unresectable lesions that are resistant to chemotherapy. Pterostilbene (PT), a naturally occurring phytoalexin, possesses a variety of pharmacologic activities, including antioxidant, cancer prevention activity and cytotoxicity to many cancers. We found that PT effectively inhibits the growth of sensitive and chemoresistant human bladder cancer cells by inducing cell cycle arrest, autophagy and apoptosis. Down-regulations of Cyclin A, B and D1 and pRB are the results of PT-induced cell cycle arrest.<br />Methods and Results: Autophagy occurred at an early stage and was observed through the formation of acidic vesicular organelles (the marker for autophagy) and microtubule-associated protein 1 light chain 3-II production. Apoptosis occurred at a later stage and was detected by Annexin V and 4',6-diamidino-2-phenylindole staining. PT-induced autophagy was triggered by the inhibition of active human protein kinase/the mammalian TOR/p70S6K pathway and activation of extracellular signal-regulated kinase pathway. Inhibition of autophagy by pretreatment with 3-methyladenine, bafilomycin A1, Beclin 1 or extracellular signal-regulated kinase short hairpin RNA enhanced PT-triggered apoptosis.<br />Conclusion: This is the first study to demonstrate that PT causes autophagy in cancer cells and suggests that PT could serve as a new and promising agent for the treatment of sensitive and chemoresistant bladder cancer cells.<br /> (Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Subjects :
- Adenine analogs & derivatives
Adenine pharmacology
Cell Line, Tumor
Down-Regulation
Gene Expression Regulation, Neoplastic
Humans
Microtubule-Associated Proteins metabolism
Mitogen-Activated Protein Kinases metabolism
Signal Transduction
Urinary Bladder Neoplasms drug therapy
Apoptosis drug effects
Autophagy drug effects
Cell Cycle drug effects
Drug Resistance, Neoplasm
Stilbenes pharmacology
Urinary Bladder Neoplasms pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1613-4133
- Volume :
- 54
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Molecular nutrition & food research
- Publication Type :
- Academic Journal
- Accession number :
- 20603834
- Full Text :
- https://doi.org/10.1002/mnfr.201000067