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

J. Biol. Chem., Vol. 280, Issue 7, 5636-5645, February 18, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/7/5636    most recent M408177200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted 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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Brusselmans, K. Articles by Swinnen, J. V. Search for Related Content PubMed PubMed Citation Articles by Brusselmans, K. Articles by Swinnen, J. V. Social Bookmarking                      What's this?

Induction of Cancer Cell Apoptosis by Flavonoids Is Associated with Their Ability to Inhibit Fatty Acid Synthase Activity^*

Koen Brusselmans, Ruth Vrolix, Guido Verhoeven, and Johannes V. Swinnen

From the Laboratory for Experimental Medicine and Endocrinology, Department of Developmental Biology, Katholieke Universiteit Leuven, B-3000, Leuven, Belgium

The consumption of food products containing high amounts of flavonoids has been reported to lower the risk of various cancers. The mechanisms underlying the cancer-protective effects of these naturally occurring polyphenolic compounds, however, remain elusive. Based on our previous finding that the cytotoxic effect of the flavanol epigallocatechin-3-gallate on prostate cancer cells correlates with its ability to inhibit fatty acid synthase (FAS, a key lipogenic enzyme overexpressed in many human cancers), we examined the anti-lipogenic effects of a panel of 18 naturally occurring polyphenolic compounds. In addition to epigallocatechin-3-gallate, five other flavonoids, more particularly luteolin, quercetin, kaempferol, apigenin, and taxifolin, also markedly inhibited cancer cell lipogenesis. Interestingly, in both prostate and breast cancer cells, a remarkable dose-response parallelism was observed between flavonoid-induced inhibition of fatty acid synthesis, inhibition of cell growth, and induction of apoptosis. In support for a role of fatty acid synthesis in these effects, the addition of exogenous palmitate, the end product of FAS, markedly suppressed the cytotoxic effects of flavonoids. Taken together, these findings indicate that the potential of flavonoids to induce apoptosis in cancer cells is strongly associated with their FAS inhibitory properties, thereby providing a new mechanism by which polyphenolic compounds may exert their cancer-preventive and antineoplastic effects.

Received for publication, July 20, 2004 , and in revised form, October 29, 2004.

^* This work was supported by Cancer Research Grants from FB Insurance (Fortis Bank), by a grant "Geconcerteerde Onderzoeksactie van de Vlaamse Gemeenschap," by research grants and a postdoctoral fellowship (to K. B.) from the Fund for Scientific Research-Flanders (Belgium) (FWO), and by a grant Interuniversity Poles of Attraction Programme-Belgian State, Prime Minister's Office, Federal Office for Scientific, Technical, and Cultural Affairs. 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: Laboratory for Experimental Medicine and Endocrinology, K. U. Leuven, Gasthuisberg, O&N, bus 902, Herestraat 49, B-3000, Leuven, Belgium. Tel.: 32-16-34-59-74; Fax: 32-16-34-59-34; E-mail: johan.swinnen{at}med.kuleuven.ac.be.

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

This article has been cited by other articles:

				D. T. Coleman, R. Bigelow, and J. A. Cardelli Inhibition of fatty acid synthase by luteolin post-transcriptionally down-regulates c-Met expression independent of proteosomal/lysosomal degradation Mol. Cancer Ther., January 1, 2009; 8(1): 214 - 224. [Abstract] [Full Text] [PDF]

				T. Migita, T. Narita, K. Nomura, E. Miyagi, F. Inazuka, M. Matsuura, M. Ushijima, T. Mashima, H. Seimiya, Y. Satoh, et al. ATP Citrate Lyase: Activation and Therapeutic Implications in Non-Small Cell Lung Cancer Cancer Res., October 15, 2008; 68(20): 8547 - 8554. [Abstract] [Full Text] [PDF]

				Y. Zhan, N. Ginanni, M. R. Tota, M. Wu, N. W. Bays, V. M. Richon, N. E. Kohl, E. S. Bachman, P. R. Strack, and S. Krauss Control of Cell Growth and Survival by Enzymes of the Fatty Acid Synthesis Pathway in HCT-116 Colon Cancer Cells Clin. Cancer Res., September 15, 2008; 14(18): 5735 - 5742. [Abstract] [Full Text] [PDF]

				X. Long, M. Fan, R. M. Bigsby, and K. P. Nephew Apigenin inhibits antiestrogen-resistant breast cancer cell growth through estrogen receptor-{alpha}-dependent and estrogen receptor-{alpha}-independent mechanisms Mol. Cancer Ther., July 1, 2008; 7(7): 2096 - 2108. [Abstract] [Full Text] [PDF]

				G. Bobe, L. B. Sansbury, P. S. Albert, A. J. Cross, L. Kahle, J. Ashby, M. L. Slattery, B. Caan, E. Paskett, F. Iber, et al. Dietary Flavonoids and Colorectal Adenoma Recurrence in the Polyp Prevention Trial Cancer Epidemiol. Biomarkers Prev., June 1, 2008; 17(6): 1344 - 1353. [Abstract] [Full Text] [PDF]

				F.-M. Lin, L.-R. Chen, E.-H. Lin, F.-C. Ke, H.-Y. Chen, M.-J. Tsai, and P.-W. Hsiao Compounds from Wedelia chinensis synergistically suppress androgen activity and growth in prostate cancer cells Carcinogenesis, December 1, 2007; 28(12): 2521 - 2529. [Abstract] [Full Text] [PDF]

				C.-T. Chiang, T.-D. Way, and J.-K. Lin Sensitizing HER2-overexpressing cancer cells to luteolin-induced apoptosis through suppressing p21WAF1/CIP1 expression with rapamycin Mol. Cancer Ther., July 1, 2007; 6(7): 2127 - 2138. [Abstract] [Full Text] [PDF]

				J. Fang, Q. Zhou, X.-l. Shi, and B.-h. Jiang Luteolin inhibits insulin-like growth factor 1 receptor signaling in prostate cancer cells Carcinogenesis, March 1, 2007; 28(3): 713 - 723. [Abstract] [Full Text] [PDF]

				K. Selvendiran, H. Koga, T. Ueno, T. Yoshida, M. Maeyama, T. Torimura, H. Yano, M. Kojiro, and M. Sata Luteolin Promotes Degradation in Signal Transducer and Activator of Transcription 3 in Human Hepatoma Cells: An Implication for the Antitumor Potential of Flavonoids. Cancer Res., May 1, 2006; 66(9): 4826 - 4834. [Abstract] [Full Text] [PDF]

				S. Shukla and S. Gupta Molecular targets for apigenin-induced cell cycle arrest and apoptosis in prostate cancer cell xenograft. Mol. Cancer Ther., April 1, 2006; 5(4): 843 - 852. [Abstract] [Full Text] [PDF]

				K. Brusselmans, E. De Schrijver, G. Verhoeven, and J. V. Swinnen RNA Interference-Mediated Silencing of the Acetyl-CoA-Carboxylase-{alpha} Gene Induces Growth Inhibition and Apoptosis of Prostate Cancer Cells Cancer Res., August 1, 2005; 65(15): 6719 - 6725. [Abstract] [Full Text] [PDF]

				P. E. Bowen Selection of Surrogate Endpoint Biomarkers to Evaluate the Efficacy of Lycopene/Tomatoes for the Prevention/Progression of Prostate Cancer J. Nutr., August 1, 2005; 135(8): 2068S - 2070S. [Full Text] [PDF]