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Cancer Research 67, 3853, April 15, 2007. doi: 10.1158/0008-5472.CAN-06-4257
© 2007 American Association for Cancer Research
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Experimental Therapeutics, Molecular Targets, and Chemical Biology

Curcumin Potentiates Antitumor Activity of Gemcitabine in an Orthotopic Model of Pancreatic Cancer through Suppression of Proliferation, Angiogenesis, and Inhibition of Nuclear Factor-{kappa}B–Regulated Gene Products

Ajaikumar B. Kunnumakkara1, Sushovan Guha2, Sunil Krishnan3, Parmeswaran Diagaradjane3, Juri Gelovani4 and Bharat B. Aggarwal1

Departments of 1 Experimental Therapeutics, 2 Gastrointestinal Medicine and Nutrition, 3 Radiation Oncology, and 4 Experimental Diagnostic Imaging, The University of Texas M. D. Anderson Cancer Center, Houston, Texas

Requests for reprints: Bharat B. Aggarwal, Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Box 143, 1515 Holcombe Boulevard, Houston, TX 77030. Phone: 713-792-3503/6459; Fax: 713-794-1613; E-mail: aggarwal{at}mdanderson.org.

Gemcitabine is currently the best treatment available for pancreatic cancer, but the disease develops resistance to the drug over time. Agents that can either enhance the effects of gemcitabine or overcome chemoresistance to the drug are needed for the treatment of pancreatic cancer. Curcumin, a component of turmeric (Curcuma longa), is one such agent that has been shown to suppress the transcription factor nuclear factor-{kappa}B (NF-{kappa}B), which is implicated in proliferation, survival, angiogenesis, and chemoresistance. In this study, we investigated whether curcumin can sensitize pancreatic cancer to gemcitabine in vitro and in vivo. In vitro, curcumin inhibited the proliferation of various pancreatic cancer cell lines, potentiated the apoptosis induced by gemcitabine, and inhibited constitutive NF-{kappa}B activation in the cells. In vivo, tumors from nude mice injected with pancreatic cancer cells and treated with a combination of curcumin and gemcitabine showed significant reductions in volume (P = 0.008 versus control; P = 0.036 versus gemcitabine alone), Ki-67 proliferation index (P = 0.030 versus control), NF-{kappa}B activation, and expression of NF-{kappa}B–regulated gene products (cyclin D1, c-myc, Bcl-2, Bcl-xL, cellular inhibitor of apoptosis protein-1, cyclooxygenase-2, matrix metalloproteinase, and vascular endothelial growth factor) compared with tumors from control mice treated with olive oil only. The combination treatment was also highly effective in suppressing angiogenesis as indicated by a decrease in CD31+ microvessel density (P = 0.018 versus control). Overall, our results suggest that curcumin potentiates the antitumor effects of gemcitabine in pancreatic cancer by suppressing proliferation, angiogenesis, NF-{kappa}B, and NF-{kappa}B–regulated gene products. [Cancer Res 2007;67(8):3853–61]




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HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
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Molecular Cancer Research Cancer Prevention Research
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Annual Meeting Education Book Meeting Abstracts Online
Copyright © 2007 by the American Association for Cancer Research.