This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kunnumakkara, A. B. Articles by Aggarwal, B. B. Search for Related Content PubMed PubMed Citation Articles by Kunnumakkara, A. B. Articles by Aggarwal, B. B.

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

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-B (NF-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-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-B activation, and expression of NF-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-B, and NF-B–regulated gene products. [Cancer Res 2007;67(8):3853–61]

This article has been cited by other articles:

				S. A. Danovi, H. H. Wong, and N. R. Lemoine Targeted therapies for pancreatic cancer Br. Med. Bull., August 27, 2008; (2008) ldn027v1. [Abstract] [Full Text] [PDF]

				Z. Tong, A. B. Kunnumakkara, H. Wang, Y. Matsuo, P. Diagaradjane, K. B. Harikumar, V. Ramachandran, B. Sung, A. Chakraborty, R. S. Bresalier, et al. Neutrophil Gelatinase-Associated Lipocalin: A Novel Suppressor of Invasion and Angiogenesis in Pancreatic Cancer Cancer Res., August 1, 2008; 68(15): 6100 - 6108. [Abstract] [Full Text] [PDF]

				G. Chadalapaka, I. Jutooru, S. Chintharlapalli, S. Papineni, R. Smith III, X. Li, and S. Safe Curcumin Decreases Specificity Protein Expression in Bladder Cancer Cells Cancer Res., July 1, 2008; 68(13): 5345 - 5354. [Abstract] [Full Text] [PDF]

				S. P. Weisberg, R. Leibel, and D. V. Tortoriello Dietary Curcumin Significantly Improves Obesity-Associated Inflammation and Diabetes in Mouse Models of Diabesity Endocrinology, July 1, 2008; 149(7): 3549 - 3558. [Abstract] [Full Text] [PDF]

				M. Schon, B. G. Wienrich, S. Kneitz, H. Sennefelder, K. Amschler, V. Vohringer, O. Weber, T. Stiewe, K. Ziegelbauer, and M. P. Schon KINK-1, a Novel Small-Molecule Inhibitor of IKK{beta}, and the Susceptibility of Melanoma Cells to Antitumoral Treatment J Natl Cancer Inst, June 18, 2008; 100(12): 862 - 875. [Abstract] [Full Text] [PDF]

				B. Feng, S. Chen, J. Chiu, B. George, and S. Chakrabarti Regulation of cardiomyocyte hypertrophy in diabetes at the transcriptional level Am J Physiol Endocrinol Metab, June 1, 2008; 294(6): E1119 - E1126. [Abstract] [Full Text] [PDF]

				A. Verma, S. Guha, P. Diagaradjane, A. B. Kunnumakkara, A. M. Sanguino, G. Lopez-Berestein, A. K. Sood, B. B. Aggarwal, S. Krishnan, J. G. Gelovani, et al. Therapeutic Significance of Elevated Tissue Transglutaminase Expression in Pancreatic Cancer Clin. Cancer Res., April 15, 2008; 14(8): 2476 - 2483. [Abstract] [Full Text] [PDF]

				A. B. Kunnumakkara, P. Diagaradjane, S. Guha, A. Deorukhkar, S. Shentu, B. B. Aggarwal, and S. Krishnan Curcumin Sensitizes Human Colorectal Cancer Xenografts in Nude Mice to {gamma}-Radiation by Targeting Nuclear Factor-{kappa}B-Regulated Gene Products Clin. Cancer Res., April 1, 2008; 14(7): 2128 - 2136. [Abstract] [Full Text] [PDF]

				M. Sun, Z. Estrov, Y. Ji, K. R. Coombes, D. H. Harris, and R. Kurzrock Curcumin (diferuloylmethane) alters the expression profiles of microRNAs in human pancreatic cancer cells Mol. Cancer Ther., March 1, 2008; 7(3): 464 - 473. [Abstract] [Full Text] [PDF]

				G. Feldmann and A. Maitra Molecular Genetics of Pancreatic Ductal Adenocarcinomas and Recent Implications for Translational Efforts J. Mol. Diagn., March 1, 2008; 10(2): 111 - 122. [Abstract] [Full Text] [PDF]