HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Gururajan, M. Articles by Bondada, S. Search for Related Content PubMed PubMed Citation Articles by Gururajan, M. Articles by Bondada, S.

Spleen Tyrosine Kinase (Syk), a Novel Target of Curcumin, Is Required for B Lymphoma Growth¹

Murali Gururajan^*,,, Trivikram Dasu^*,, Seif Shahidain^*,, C. Darrell Jennings, Darrell A. Robertson, Vivek M. Rangnekar^*,,¶ and Subbarao Bondada^2,*,,,¶

^* Department of Microbiology, Immunology, and Molecular Genetics, Sanders Brown Center on Aging, Graduate Center for Toxicology, Department of Pathology and Laboratory Medicine, and ^¶ Markey Cancer Center, University of Kentucky, Lexington, KY 40536

Curcumin (diferuloylmethane), a component of dietary spice turmeric (Curcuma longa), has been shown in recent studies to have therapeutic potential in the treatment of cancer, diabetes, arthritis, and osteoporosis. We investigated the ability of curcumin to modulate the growth of B lymphomas. Curcumin inhibited the growth of both murine and human B lymphoma in vitro and murine B lymphoma in vivo. We also demonstrate that curcumin-mediated growth inhibition of B lymphoma is through inhibition of the survival kinase Akt and its key target Bad. However, in vitro kinase assays show that Akt is not a direct target of curcumin. We identified a novel target for curcumin in B lymphoma viz spleen tyrosine kinase (Syk). Syk is constitutively activated in primary tumors and B lymphoma cell lines and curcumin down-modulates Syk activity accompanied by down-regulation of Akt activation. Moreover, we show that overexpression of Akt, a target of Syk, or Bcl-x_L, a target of Akt can overcome curcumin-induced apoptosis of B lymphoma cells. These observations suggest a novel growth promoting role for Syk in lymphoma cells.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health Grants AI 21490, AG 05731, and CA 92372 (to S.B.).

² Address correspondence and reprint requests to Dr. Subbarao Bondada, Center on Aging, University of Kentucky, Room 329A, Sanders Brown Building, Lexington, KY 40536-0230. E-mail address: bondada{at}uky.edu

³ Abbreviations used in this paper: NHL, non-Hodgkin’s lymphoma; DLBCL, diffuse large B cell lymphoma; mTOR, mammalian target of rapamycin; Syk, spleen tyrosine kinase; PI, propidium iodide; MyrAkt, myristoylated Akt; GSK, glycogen synthase kinase-3; PDK, phosphoinositide dependent kinase-1; siRNA, small interfering RNA; PARP, poly(ADP-ribose) polymerase.

This article has been cited by other articles:

				L. Chen, S. Monti, P. Juszczynski, J. Daley, W. Chen, T. E. Witzig, T. M. Habermann, J. L. Kutok, and M. A. Shipp SYK-dependent tonic B-cell receptor signaling is a rational treatment target in diffuse large B-cell lymphoma Blood, February 15, 2008; 111(4): 2230 - 2237. [Abstract] [Full Text] [PDF]

				A. Vojdani, F. Hebroni, Y. Raphael, J. Erde, and B. Raxlen Novel Diagnosis of Lyme Disease: Potential for CAM Intervention Evid. Based Complement. Altern. Med., October 15, 2007; (2007) nem138v1. [Abstract] [Full Text] [PDF]