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

Hosono, Takashi; Fukao, Tomomi; Ogihara, Jun; Ito, Yoshimasa; Shiba, Hiroshi; Seki, Taiichiro; Ariga, Toshio

doi:10.1074/jbc.m507127200

Cited by 217 publications

(164 citation statements)

References 39 publications

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“…Using 80 and 160 M of ITC (ITC: tubulin cysteine ϭ 1:1 and 2:1), the numbers of thiols modified by BITC were 9.5 and 11.7, PEITC 6.2 and 9.1, and SFN 2.6 and 3.8, respectively. We used diallyl trisulfide as an internal control, and the results were in excellent agreement with that reported previously (17).…”

Section: Bitc Peitc and Sfn Altered Tubulin Secondary And Tertiary supporting

confidence: 77%

Covalent Binding to Tubulin by Isothiocyanates

Xiao

Hood

et al. 2008

Journal of Biological Chemistry

187

130

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Isothiocyanates (ITCs) found in cruciferous vegetables, including benzyl-ITC (BITC), phenethyl-ITC (PEITC), and sulforaphane (SFN), inhibit carcinogenesis in animal models and induce apoptosis and cell cycle arrest in various cell types. The biochemical mechanisms of cell growth inhibition by ITCs are not fully understood. Our recent study showed that ITC binding to intracellular proteins may be an important initiating event for the induction of apoptosis. However, the specific protein target(s) and molecular mechanisms were not identified. In this study, two-dimensional gel electrophoresis of human lung cancer A549 cells treated with radiolabeled PEITC and SFN revealed that tubulin may be a major in vivo binding target for ITC. We examined whether binding to tubulin by ITCs could lead to cell growth arrest. The proliferation of A549 cells was significantly reduced by ITCs, with relative activities of BITC > PEITC > SFN. All three ITCs also induced mitotic arrest and apoptosis with the same order of activity. We found that ITCs disrupted microtubule polymerization in vitro and in vivo with the same order of potency. Mass spectrometry demonstrated that cysteines in tubulin were covalently modified by ITCs. Ellman assay results indicated that the modification levels follow the same order, BITC > PEITC > SFN. Together, these results support the notion that tubulin is a target of ITCs and that ITCtubulin interaction can lead to downstream growth inhibition. This is the first study directly linking tubulin-ITC adduct formation to cell growth inhibition.

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Section: Bitc Peitc and Sfn Altered Tubulin Secondary And Tertiary supporting

confidence: 77%

Covalent Binding to Tubulin by Isothiocyanates

Xiao

Hood

et al. 2008

Journal of Biological Chemistry

187

130

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“…Previous epidemiological and scientific studies have indicated that plant-derived phytochemicals may be beneficial in the prevention and treatment of cancer (3)(4)(5). Resveratrol is a polyphenolic compound, which is present in grapes (red wine), knotweed, peanuts, mulberries and other plants.…”

Section: Introductionmentioning

confidence: 99%

Inhibitory effects of resveratrol on the adhesion, migration and invasion of human bladder cancer cells

Bai

Yang

Zhang

et al. 2016

Molecular Medicine Reports

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Abstract.Resveratrol is a polyphenolic compound, which has been revealed to induce apoptosis in numerous human cancer cells; however, the effects of resveratrol on the migration and invasion of human bladder cancer cells have not been reported. The present study aimed to evaluate the anti-metastatic potential of resveratrol against bladder cancer and its mechanism of action. The results indicated that resveratrol inhibits the adhesion, migration and invasion of bladder cancer cells in a dose-dependent manner. Resveratrol was shown to significantly inhibit the expression and secretion of matrix metalloproteinase (MMP)-2 and MMP-9 in bladder cancer cells. Furthermore, resveratrol suppressed the phosphorylation of c-Jun N-terminal kinase and extracellular signal-regulated protein kinase. In conclusion, the present study is the first, to the best of our knowledge, to demonstrate that resveratrol may be considered a novel anticancer agent for the treatment of bladder cancer via the inhibition of migration and invasion. IntroductionBladder cancer is the fourth most common type of cancer, and was the cause of >11,510 cases of cancer-associated mortality among men in the USA in 2014 (1). The majority of bladder cancer cases are noninvasive, low-grade transitional cell carcinoma (TCC); however, ≤30% of all diagnosed tumors are classified as invasive TCC, which is associated with high mortality (2). Notably, among all of the various types of cancer, bladder cancer exhibits a significantly high incidence of recurrence post-treatment, and therefore is recognized as the most expensive cancer to treat. Due to the high prevalence and frequent tumor recurrence associated with bladder cancer, the exploration of preventative strategies is required.Previous epidemiological and scientific studies have indicated that plant-derived phytochemicals may be beneficial in the prevention and treatment of cancer (3-5). Resveratrol is a polyphenolic compound, which is present in grapes (red wine), knotweed, peanuts, mulberries and other plants. Numerous studies have suggested that resveratrol may prevent the progression of various pathologies, including vascular diseases, ischemic injuries, cancer and neurodegenerative disorders (6-8). Furthermore, it has previously been confirmed that resveratrol exerts antiproliferative and/or apoptotic effects on leukemia, prostate, breast and colon cancers cells in vitro (9-12). Previous studies regarding the anticancer effects of resveratrol have focused on its anti-invasive and anti-metastatic activities (13-15). However, to the best of our knowledge, there is currently no evidence as to whether resveratrol may inhibit the migration and invasion of human bladder cancer cells.Metastasis is one of the hallmarks of advanced cancer progression, and cancer cell migration and invasion are crucial events in bladder cancer metastasis. Matrix metalloproteinases (MMPs), including MMP-2 and MMP-9, degrade the basement membrane and extracellular matrix (ECM), and are therefore considered crucial proteolytic protei...

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“…Tubulin has 20 cysteine and 24 histidine residues per dimer. Studies on residue-selective alkylation or oxidative modification have demonstrated that some of these residues are important for polymerization (Hosono et al, 2005;Kuriyama and Sakai, 1974;Mellon and Rebhun, 1976;Oliver et al, 1976;Rai and Wolff, 1998).…”

Section: Introductionmentioning

confidence: 99%

Mechanism of Destruction of Microtubule Structures by 4-Hydroxy-2-Nonenal

Kokubo

Nagatani

Hiroki

et al. 2008

Cell Struct. Funct.

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ABSTRACT. A major end product of lipid peroxidation, 4-hydroxy-2-nonenal (HNE), is an electrophilic alkenal and produces Michael adducts with cellular proteins. It is known that exposure of cultured cells to HNE causes rapid disappearance of microtubule networks. In this study we addressed the mechanism. Immunochemical studies revealed that HNE preferentially modified α-tubulin in rat primary neuronal cells, PC12 cells, and rat fibroblast cell line 3Y1 cells. This was morphologically associated with the disappearance of microtubule structures in those cells. In a purified rat brain microtubule fraction, HNE modified unpolymerized tubulin and impaired its polymerizability, with a concomitant increase in insolubilized tubulin. Nevertheless, HNE had a marginal effect on the stability of pre-polymerized microtubules. These results suggest that disruption of microtubule assembly as a result of HNE modification of unpolymerized tubulin, rather than destruction of assembled microtubules, is responsible for the disappearance of microtubule structures in cells exposed to HNE.

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

Cited by 217 publications

References 39 publications

Covalent Binding to Tubulin by Isothiocyanates

Covalent Binding to Tubulin by Isothiocyanates

Inhibitory effects of resveratrol on the adhesion, migration and invasion of human bladder cancer cells

Mechanism of Destruction of Microtubule Structures by 4-Hydroxy-2-Nonenal

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