Alkenyl group is responsible for the disruption of microtubule network formation in human colon cancer cell line HT-29 cells
| Autor: | Taiichiro Seki, Tomomi Hosono-Fukao, Yuji Iitsuka, Rie Tanaka, Toyohiko Ariga, Kahoru Inada, Takashi Hosono, Isao Hasegawa, Haruhisa Yamada |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
G2 Phase
Cancer Research Cell cycle checkpoint Allyl compound Mitosis Spindle Apparatus Adenocarcinoma Alkenes Sulfides Biology Microtubules chemistry.chemical_compound Humans Drug Interactions Cysteine Disulfides Buthionine Sulfoximine General Medicine Glutathione Cell cycle Allyl Compounds Diallyl trisulfide Tubulin chemistry Biochemistry Colonic Neoplasms Cancer cell biology.protein Dimethyl trisulfide Cancer Prevention HT29 Cells Cell Division |
| Zdroj: | Carcinogenesis |
| ISSN: | 1460-2180 0143-3334 |
| DOI: | 10.1093/carcin/bgn124 |
| Popis: | Alk(en)yl trisulfides (R-SSS-R') are organosulfur compounds produced by crushed garlic and other Allium vegetables. We found that these compounds exhibit potent anticancer effects through the reaction with microtubules, causing cell cycle arrest. Nine alk(en)yl trisulfides including dimethyl trisulfide, diethyl trisulfide, dipropyl trisulfide (DPTS), dibutyl trisulfide, dipentyl trisulfide, diallyl trisulfide (DATS), dibutenyl trisulfide, dipentenyl trisulfide and allyl methyl trisulfide were synthesized and added to cultures of HT-29 human colon cancer cells at a concentration of 10 muM. The trisulfides with alkenyl groups such as DATS, but not those with alkyl groups, induced rapid microtubule disassembly at 30-60 min as well as cell cycle arrest during the mitotic phase approximately at 4 h after the treatment. Both DATS-induced microtubule disassembly and the cell cycle arrest were cancelled by the simultaneous treatment of the cancer cells with 2 mM L-cysteine, glutathione (GSH) or N-acetyl-L-cysteine. Reciprocally, L-buthionine-(S,R)-sulfoximine (500 muM), an inhibitor of GSH synthesis, enhanced the power of DATS in inducing the cell cycle arrest. These results indicate that alk(en)yl trisulfide react with sulfhydryl groups in cysteine residues of cellular proteins such as microtubule proteins. Thus, the present study provides evidence that trisulfides with alkenyl groups have potent anticancer activities, at least in part, directed toward microtubules. These findings suggest that alkenyl trisulfides and their structurally related compounds may provide novel and effective anticancer agents. |
| Databáze: | OpenAIRE |
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