NDLI: Carnosol, a Dietary Diterpene, Displays Growth Inhibitory Effects in Human Prostate Cancer PC3 Cells Leading to G$_{2}$-Phase Cell Cycle Arrest and Targets the 5′-AMP-Activated Protein Kinase (AMPK) Pathway

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Carnosol, a Dietary Diterpene, Displays Growth Inhibitory Effects in Human Prostate Cancer PC3 Cells Leading to G$_{2}$-Phase Cell Cycle Arrest and Targets the 5′-AMP-Activated Protein Kinase (AMPK) Pathway

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Carnosol, a Dietary Diterpene, Displays Growth Inhibitory Effects in Human Prostate Cancer PC3 Cells Leading to G$_{2}$-Phase Cell Cycle Arrest and Targets the 5′-AMP-Activated Protein Kinase (AMPK) Pathway

Content Provider	Springer Nature Link
Author	Johnson, Jeremy J. Syed, Deeba N. Heren, Chenelle R. Suh, Yewseok Adhami, Vaqar M. Mukhtar, Hasan
Copyright Year	2008
Abstract	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.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.Using an MTT assay we found that carnosol (10–70 μM) decreases cell viability in a time and dose-dependent manner. Further analysis using flow cytometry as well as biochemical analysis identified G$_{2}$-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.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.
Starting Page	2125
Ending Page	2134
Page Count	10
File Format	PDF
ISSN	07248741
Journal	Pharmaceutical Research
Volume Number	25
Issue Number	9
e-ISSN	1573904X
Language	English
Publisher	Springer US
Publisher Date	2008-02-21
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Akt AMPK carnosol chemoprevention mTOR PC3 prostate cancer rosemary Biomedical Engineering Medical Law Biochemistry Pharmacy Pharmacology/Toxicology
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry Pharmacology Molecular Medicine Pharmacology (medical) Biotechnology Pharmaceutical Science

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Carnosol, a Dietary Diterpene, Displays Growth Inhibitory Effects in Human Prostate Cancer PC3 Cells Leading to G$_{2}$-Phase Cell Cycle Arrest and Targets the 5′-AMP-Activated Protein Kinase (AMPK) Pathway

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Carnosol, a Dietary Diterpene, Displays Growth Inhibitory Effects in Human Prostate Cancer PC3 Cells Leading to G$_{2}$-Phase Cell Cycle Arrest and Targets the 5′-AMP-Activated Protein Kinase (AMPK) Pathway