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Pharm Res. 2008 Sep;25(9):2125-34. doi: 10.1007/s11095-008-9552-0. Epub 2008 Feb 21.

Carnosol, a dietary diterpene, displays growth inhibitory effects in human prostate cancer PC3 cells leading to G2-phase cell cycle arrest and targets the 5'-AMP-activated protein kinase (AMPK) pathway.

Author information

1
Center for Women's Health Research, University of Wisconsin, School of Medicine and Public Health, Madison, Wisconsin, USA.

Abstract

PURPOSE:

This study examines the anti-cancer effect of carnosol in human prostate cancer PC3 cells and its role in modulating multiple signaling pathways associated with carcinogenesis.

METHODS:

PC3 cells were treated with carnosol and were evaluated using a flow cytometry, a protein array and Western blot analysis to identify signaling pathways targeted by carnosol.

RESULTS:

Using an MTT assay we found that carnosol (10-70 microM) decreases cell viability in a time and dose-dependent manner. Further analysis using flow cytometry as well as biochemical analysis identified G2-phase cell cycle arrest. To establish a more precise mechanism, we performed a protein array that evaluated 638 proteins involved in cell signaling pathways. The protein array identified 5'-AMP-activated protein kinase (AMPK), a serine/threonine protein kinase involved in the regulation of cellular energy balance as a potential target. Further downstream effects consistent with cancer inhibition included the modulation of the mTOR/HSP70S6k/4E-BP1 pathway. Additionally, we found that carnosol targeted the PI3K/Akt pathway in a dose dependent manner.

CONCLUSIONS:

These results suggest that carnosol targets multiple signaling pathways that include the AMPK pathway. The ability of carnosol to inhibit prostate cancer in vitro suggests carnosol may be a novel agent for the management of PCa.

PMID:
18286356
PMCID:
PMC2994272
DOI:
10.1007/s11095-008-9552-0
[Indexed for MEDLINE]
Free PMC Article

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