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

J. Biol. Chem., Vol. 280, Issue 50, 41487-41493, December 16, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/50/41487    most recent M507127200v1 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 Hosono, T. Articles by Ariga, T. Search for Related Content PubMed PubMed Citation Articles by Hosono, T. Articles by Ariga, T. Social Bookmarking                      What's this?

Diallyl Trisulfide Suppresses the Proliferation and Induces Apoptosis of Human Colon Cancer Cells through Oxidative Modification of -Tubulin^*

Takashi Hosono1, Tomomi Fukao2, Jun Ogihara, Yoshimasa Ito, Hajime Shiba, Taiichiro Seki3, and Toyohiko Ariga

From the Departments of Applied Life Sciences and Bioresource Utilization, Nihon University Graduate School of Bioresource Sciences, Kanagawa 252-8510, Japan

Allyl sulfides are characteristic flavor components obtained from garlic. These sulfides are thought to be responsible for their epidemiologically proven anticancer effect on garlic eaters. This study was aimed at clarifying the molecular basis of this anticancer effect of garlic by using human colon cancer cell lines HCT-15 and DLD-1. The growth of the cells was significantly suppressed by diallyl trisulfide (DATS, HCT-15 IC₅₀ = 11.5 µM, DLD-1 IC₅₀ = 13.3 µM); however, neither diallyl monosulfide nor diallyl disulfide showed such an effect. The proportion of HCT-15 and that of DLD-1 cells residing at the G₁ and S phases were decreased by DATS, and their populations at the G₂/M phase were markedly increased for up to 12 h. The cells with a sub-G₁ DNA content were increased thereafter. Caspase-3 activity was also dramatically increased by DATS. Fluorescence-activated cell sorter analysis performed on the cells arrested at the G₁/S boundary revealed cell cycle-dependent induction of apoptosis through the transition of the G₂/M phase to the G₁ phase by DATS. DATS inhibited tubulin polymerization in an in vitro cell-free system. DATS disrupted microtubule network formation of the cells, and microtubule fragments could be seen at the interphase. Peptide mass mapping by liquid chromatography-tandem mass spectrometry analysis for DATS-treated tubulin demonstrated that there was a specific oxidative modification of cysteine residues Cys-12 and Cys-354 to form S-allylmercaptocysteine with a peptide mass increase of 72.1 Da. The potent antitumor activity of DATS was also demonstrated in nude mice bearing HCT-15 xenografts. This is the first paper describing intracellular target molecules directly modified by garlic components.

Received for publication, June 30, 2005 , and in revised form, September 27, 2005.

^* This work was supported by grants from the program grants-in aid for Scientific Research on Priority Areas (C; Cancer) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan and by funds from the Academic Frontier Project from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (to T. S.), and by grants-in aid for Scientific Research (B) (to T. A.) and (C) (to T. S.) from the Japan Society for the Promotion of Science. 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 Supported by a Japan Society for the Promotion of Science Fellowship and a Fellowship from the Center of Excellence (COE) Program in the 21st Century in Japan.

² Supported by a Fellowship from the COE Program in the 21st Century in Japan.

³ To whom correspondence should be addressed: Laboratory of Nutrition and Physiology, Dept. of Applied Life Sciences, Nihon University Graduate School of Bioresource Sciences, Kanagawa 252-8510, Japan. Tel./Fax: 81-466-84-3949; E-mail: tseki{at}brs.nihon-u.ac.jp.

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

This article has been cited by other articles:

				S. V. Singh, A. A. Powolny, S. D. Stan, D. Xiao, J. A. Arlotti, R. Warin, E.-R. Hahm, S. W. Marynowski, A. Bommareddy, D. M. Potter, et al. Garlic Constituent Diallyl Trisulfide Prevents Development of Poorly Differentiated Prostate Cancer and Pulmonary Metastasis Multiplicity in TRAMP Mice Cancer Res., November 15, 2008; 68(22): 9503 - 9511. [Abstract] [Full Text] [PDF]

				G. Filomeni, G. Rotilio, and M. R. Ciriolo Molecular Transduction Mechanisms of the Redox Network Underlying the Antiproliferative Effects of Allyl Compounds from Garlic J. Nutr., November 1, 2008; 138(11): 2053 - 2057. [Abstract] [Full Text] [PDF]

				L. Mi, Z. Xiao, B. L. Hood, S. Dakshanamurthy, X. Wang, S. Govind, T. P. Conrads, T. D. Veenstra, and F.-L. Chung Covalent Binding to Tubulin by Isothiocyanates: A MECHANISM OF CELL GROWTH ARREST AND APOPTOSIS J. Biol. Chem., August 8, 2008; 283(32): 22136 - 22146. [Abstract] [Full Text] [PDF]

				T. Hosono, T. Hosono-Fukao, K. Inada, R. Tanaka, H. Yamada, Y. Iitsuka, T. Seki, I. Hasegawa, and T. Ariga Alkenyl group is responsible for the disruption of microtubule network formation in human colon cancer cell line HT-29 cells Carcinogenesis, July 1, 2008; 29(7): 1400 - 1406. [Abstract] [Full Text] [PDF]

				K. Huber, P. Patel, L. Zhang, H. Evans, A. D. Westwell, P. M. Fischer, S. Chan, and S. Martin 2-[(1-Methylpropyl)dithio]-1H-imidazole inhibits tubulin polymerization through cysteine oxidation Mol. Cancer Ther., January 1, 2008; 7(1): 143 - 151. [Abstract] [Full Text] [PDF]

				S. N. T. Ngo, D. B. Williams, L. Cobiac, and R. J. Head Does Garlic Reduce Risk of Colorectal Cancer? A Systematic Review J. Nutr., October 1, 2007; 137(10): 2264 - 2269. [Abstract] [Full Text] [PDF]

				L. Mi, X. Wang, S. Govind, B. L. Hood, T. D. Veenstra, T. P. Conrads, D. T. Saha, R. Goldman, and F.-L. Chung The Role of Protein Binding in Induction of Apoptosis by Phenethyl Isothiocyanate and Sulforaphane in Human Non-Small Lung Cancer Cells Cancer Res., July 1, 2007; 67(13): 6409 - 6416. [Abstract] [Full Text] [PDF]

				Y.-A. Kim, D. Xiao, H. Xiao, A. A. Powolny, K. L. Lew, M. L. Reilly, Y. Zeng, Z. Wang, and S. V. Singh Mitochondria-mediated apoptosis by diallyl trisulfide in human prostate cancer cells is associated with generation of reactive oxygen species and regulated by Bax/Bak Mol. Cancer Ther., May 1, 2007; 6(5): 1599 - 1609. [Abstract] [Full Text] [PDF]

				A. Herman-Antosiewicz, S. D. Stan, E.-R. Hahm, D. Xiao, and S. V. Singh Activation of a novel ataxia-telangiectasia mutated and Rad3 related/checkpoint kinase 1-dependent prometaphase checkpoint in cancer cells by diallyl trisulfide, a promising cancer chemopreventive constituent of processed garlic Mol. Cancer Ther., April 1, 2007; 6(4): 1249 - 1261. [Abstract] [Full Text] [PDF]

				D. Xiao, K. L. Lew, Y.-A. Kim, Y. Zeng, E.-R. Hahm, R. Dhir, and S. V. Singh Diallyl Trisulfide Suppresses Growth of PC-3 Human Prostate Cancer Xenograft In vivo in Association with Bax and Bak Induction. Clin. Cancer Res., November 15, 2006; 12(22): 6836 - 6843. [Abstract] [Full Text] [PDF]

				J. Antosiewicz, A. Herman-Antosiewicz, S. W. Marynowski, and S. V. Singh c-Jun NH2-Terminal Kinase Signaling Axis Regulates Diallyl Trisulfide-Induced Generation of Reactive Oxygen Species and Cell Cycle Arrest in Human Prostate Cancer Cells. Cancer Res., May 15, 2006; 66(10): 5379 - 5386. [Abstract] [Full Text] [PDF]