Alkenyl group is responsible for the disruption of microtubule network formation in human colon cancer cell line HT-29 cells

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 μM. 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 μM), 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

Cinnamon extract improves abnormalities in glucose tolerance by decreasing Acyl-CoA synthetase long-chain family 1 expression in adipocytes

Abstract We previously demonstrated that cinnamon extract (CE) alleviates streptozotocin-induced type 1 diabetes in rats. The present study aimed to elucidate the detailed molecular target of cinnamon in cultured adipocytes and epididymal adipose tissue of type 2 diabetes model mice. Two-dimensional gel electrophoresis was employed to determine the molecular target of cinnamon in adipocytes. The function of Acyl-CoA synthetase long-chain family-1 (ACSL1), a molecular target of cinnamon that was identified in this study, was further investigated in 3T3-L1 adipocytes using specific inhibitors. Type 2 diabetes model mice (KK-Ay/TaJcl) were used to investigate the effect of CE on glucose tolerance, ACSL1 expression, and related signal molecules in vivo. CE decreased ACSL1 mRNA and protein expression in 3T3-L1 adipocytes but increased glucose uptake and AMPK signaling activation; moreover, a similar effect was observed with an ACSL1 inhibitor. CE improved glucose tolerance and downregulated ACSL1 in mice adipose tissue in vivo. ACSL1 was demonstrated as a molecular target of CE in type 2 diabetes both in a cell culture system and diabetic mouse model

Cell cycle progression of HT-29 cells cultured in the presence of alk(en)yl trisulfides having various structures

HT-29 cells were cultured in the presence or absence of alkyl trisulfides (dimethyl trisulfide, diethyl trisulfide, DPTS, dibutyl trisulfide and dipentyl trisulfide), alkenyl trisulfides (DATS, dibutenyl trisulfide and dipentenyl trisulfide) or mixed ank(en)yl trisulfide (allyl methyl trisulfide) at a concentration of 10 μM for 12 h. Then, the cell cycle distribution in G/M phase was analyzed by using a flow cytometer, as described in Materials and Methods (panel ). Values are the mean ± SE of three independent experiments. ** ( <p><b>Copyright information:</b></p><p>Taken from "Alkenyl group is responsible for the disruption of microtubule network formation in human colon cancer cell line HT-29 cells"</p><p></p><p>Carcinogenesis 2008;29(7):1400-1406.</p><p>Published online 29 May 2008</p><p>PMCID:PMC2500214.</p><p></p

Induction of mitotic arrest by DATS through the inhibition of mitotic spindle formation

Detection of Ser10-phosphorylated histone H3, a sensitive marker for cells at the M phase, was detected in HT-29 cells cultured with DATS (10 μM) for 12 h by using a flow cytometer (panel ). Spindle formation of HT-29 cells cultured with vehicle or DATS (10 μM) was assessed by the immunofluorescence method using anti-β-tubulin antibody, as described in Materials and Methods (green; panel ). The nucleus was counterstained with propidium iodide (magenta). Scale bar 20 μm.<p><b>Copyright information:</b></p><p>Taken from "Alkenyl group is responsible for the disruption of microtubule network formation in human colon cancer cell line HT-29 cells"</p><p></p><p>Carcinogenesis 2008;29(7):1400-1406.</p><p>Published online 29 May 2008</p><p>PMCID:PMC2500214.</p><p></p

BSO enhanced and sustained the DATS-induced cell cycle arrest but had little influence on DPTS-treated cells

HT-29 cells were pretreated with 500 μM BSO for 24 h and then the cells were treated with 10 μM DATS ( and ) or DPTS ( and ) for the times as indicated. The cell cycle distribution of the cells was analyzed by using a flow cytometer.<p><b>Copyright information:</b></p><p>Taken from "Alkenyl group is responsible for the disruption of microtubule network formation in human colon cancer cell line HT-29 cells"</p><p></p><p>Carcinogenesis 2008;29(7):1400-1406.</p><p>Published online 29 May 2008</p><p>PMCID:PMC2500214.</p><p></p