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

J. Biol. Chem., Vol. 280, Issue 20, 20059-20068, May 20, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/20/20059    most recent M410670200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend 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 Choudhuri, T. Articles by Sa, G. Search for Related Content PubMed PubMed Citation Articles by Choudhuri, T. Articles by Sa, G. Social Bookmarking                      What's this?

Curcumin Selectively Induces Apoptosis in Deregulated Cyclin D1-expressed Cells at G₂ Phase of Cell Cycle in a p53-dependent Manner^*

Tathagata Choudhuri, Suman Pal, Tanya Das, and Gaurisankar Sa

From the Bose Institute, P-1/12 Calcutta Improvement Trust Scheme VII M, Kolkata 700 054, India

Curcumin (diferuloylmethane) is known to induce apoptosis in tumor cells. In asynchronous cultures, with time-lapse video-micrography in combination with quantitative fluorescence microscopy, we have demonstrated that curcumin induces apoptosis at G₂ phase of cell cycle in deregulated cyclin D1-expressed mammary epithelial carcinoma cells, leaving its normal counterpart unaffected. In our search toward delineating the molecular mechanisms behind such differential activities of curcumin, we found that it selectively increases p53 expression at G₂ phase of carcinoma cells and releases cytochrome c from mitochondria, which is an essential requirement for apoptosis. Further experiments using p53-null as well as dominant-negative and wild-type p53-transfected cells have established that curcumin induces apoptosis in carcinoma cells via a p53-dependent pathway. On the other hand, curcumin reversibly inhibits normal mammary epithelial cell cycle progression by down-regulating cyclin D1 expression and blocking its association with Cdk4/Cdk6 as well as by inhibiting phosphorylation and inactivation of retinoblastoma protein. In addition, curcumin significantly up-regulates cell cycle inhibitory protein (p21Waf-1) in normal cells and arrests them in G₀ phase of cell cycle. Therefore, these cells escape from curcumin-induced apoptosis at G₂ phase. Interestingly, these processes remain unaffected by curcumin in carcinoma cells where cyclin D1 expression is high. Similarly, in ectopically overexpressed system, curcumin cannot down-regulate cyclin D1 and thus block cell cycle progression. Hence, these cells progress into G₂ phase and undergo apoptosis. These observations together suggest that curcumin may have a possible therapeutic potential in breast cancer patients.

Received for publication, September 16, 2004 , and in revised form, February 4, 2005.

^* This work was supported by research grants from Department of Science and Technology (Government of India). 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.

To whom correspondence should be addressed: Bose Institute, P-1/12 CIT Scheme VII M, Kolkata 700 054, India. Tel.: 91-33-2337-9416 or 91-33-2337-9544; Fax: 91-33-2334-3886; E-mail: gauri{at}boseinst.ernet.in.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				H. Hu, H.-J. Lee, C. Jiang, J. Zhang, L. Wang, Y. Zhao, Q. Xiang, E.-O. Lee, S.-H. Kim, and J. Lu Penta-1,2,3,4,6-O-galloyl-{beta}-D-glucose induces p53 and inhibits STAT3 in prostate cancer cells in vitro and suppresses prostate xenograft tumor growth in vivo Mol. Cancer Ther., September 1, 2008; 7(9): 2681 - 2691. [Abstract] [Full Text] [PDF]

				T. Choudhuri, S. C. Verma, K. Lan, M. Murakami, and E. S. Robertson The ATM/ATR Signaling Effector Chk2 Is Targeted by Epstein-Barr Virus Nuclear Antigen 3C To Release the G2/M Cell Cycle Block J. Virol., June 15, 2007; 81(12): 6718 - 6730. [Abstract] [Full Text] [PDF]

				S. Bhattacharyya, D. Mandal, B. Saha, G. S. Sen, T. Das, and G. Sa Curcumin Prevents Tumor-induced T Cell Apoptosis through Stat-5a-mediated Bcl-2 Induction J. Biol. Chem., June 1, 2007; 282(22): 15954 - 15964. [Abstract] [Full Text] [PDF]

				S. Balasubramanian and R. L. Eckert Curcumin Suppresses AP1 Transcription Factor-dependent Differentiation and Activates Apoptosis in Human Epidermal Keratinocytes J. Biol. Chem., March 2, 2007; 282(9): 6707 - 6715. [Abstract] [Full Text] [PDF]

				S. Bhattacharyya, D. Mandal, G. S. Sen, S. Pal, S. Banerjee, L. Lahiry, J. H. Finke, C. S. Tannenbaum, T. Das, and G. Sa Tumor-Induced Oxidative Stress Perturbs Nuclear Factor-{kappa}B Activity-Augmenting Tumor Necrosis Factor-{alpha}-Mediated T-Cell Death: Protection by Curcumin Cancer Res., January 1, 2007; 67(1): 362 - 370. [Abstract] [Full Text] [PDF]

				R. Kamath, Z. Jiang, G. Sun, J. C. Yalowich, and R. Baskaran c-Abl Kinase Regulates Curcumin-Induced Cell Death through Activation of c-Jun N-Terminal Kinase Mol. Pharmacol., January 1, 2007; 71(1): 61 - 72. [Abstract] [Full Text] [PDF]

				K. Lan, T. Choudhuri, M. Murakami, D. A. Kuppers, and E. S. Robertson Intracellular Activated Notch1 Is Critical for Proliferation of Kaposi's Sarcoma-Associated Herpesvirus-Associated B-Lymphoma Cell Lines In Vitro. J. Virol., July 1, 2006; 80(13): 6411 - 6419. [Abstract] [Full Text] [PDF]

				D. Chirnomas, T. Taniguchi, M. de la Vega, A. P. Vaidya, M. Vasserman, A.-R. Hartman, R. Kennedy, R. Foster, J. Mahoney, M. V. Seiden, et al. Chemosensitization to cisplatin by inhibitors of the Fanconi anemia/BRCA pathway. Mol. Cancer Ther., April 1, 2006; 5(4): 952 - 961. [Abstract] [Full Text] [PDF]

				D. R. Yance Jr and S. M. Sagar Targeting angiogenesis with integrative cancer therapies. Integr Cancer Ther, March 1, 2006; 5(1): 9 - 29. [Abstract] [PDF]

				J. Fang, J. Lu, and A. Holmgren Thioredoxin Reductase Is Irreversibly Modified by Curcumin: A NOVEL MOLECULAR MECHANISM FOR ITS ANTICANCER ACTIVITY J. Biol. Chem., July 1, 2005; 280(26): 25284 - 25290. [Abstract] [Full Text] [PDF]