Mechanisms of Taxotere-induced apoptosis in or a squamous cell carcinoma.

泰索帝诱导鳞状细胞癌凋亡的机制。

• 批准号: 16390577
• 负责人: RIKIISHI Hidemi
• 金额: $ 6.66万
• 依托单位: TOHOKU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16390577/
• 关键词: Taxotere; Selenium compounds; Cisplatin; Apoptosis; Caspase; Mitochondria; Cytochrome C; Reactive oxygen species; 併用療法; epigenetics; グルタチオン; 増強剤; 膜電位

Apoptosis induced by Taxotere that interferes with microtubule polymerization dynamics and is used clinically to treat advanced cancers, has not been fully defined in squamous cell carcinoma. In this study, apoptotic events involved in Taxotere treatment were investigated. When the human oral squamous cell carcinoma cell line HSC-3 was exposed to Taxotere for 72 h, a dose-dependent effect was observed in apoptosis using the TUNEL method. We observed activation of caspase cascade including activities like caspase-3,-8,and-9. And the pan-caspase inhibitor z-VAD-fmk prevented apoptosis induced by Taxotere (0.1 μM), showing participation of caspases in this process. Since an antagonistic CD95-antibody (ZB4) exerted no effect on Taxotere-induced apoptosis, CD95/CD95L interaction was not involved in this pathway. The caspase-8-like activity was inhibited not only by IETD-fmk (caspase-8) but also by DEVD-fmk (caspase-3). The results indicate that the caspase-8-like activation occurred downstream of DEVDase. Taxotere promoted the formation of reactive oxygen species (ROS) in mitochondria, and preincubation of cells with anti-oxidants such as N-acetyl cysteine and pyrrolidine dithiocarbamate, protected against apoptosis mediated by Taxotere. Furthermore, treatment with Taxotere elicited reduction of mitochondrial membrane potential, and release of cytochrome c to cytosol, after 48 h of treatment. We observed binding activity to NF-κB consensus site and interference with the mitochondrial function via NF-κB after Taxotere treatment. Preventing pro-apoptotic property of NF-κB inhibited Taxotere-induced apoptosis. Thus, these results suggest that, following the activation of NF-κB by Taxotere, apoptosis is elicited through a mitochondria-dependent pathway

泰索帝诱导的细胞凋亡干扰微管聚合动力学，临床上用于治疗晚期癌症，但在鳞状细胞癌中尚未完全确定。在这项研究中，涉及泰索帝治疗的凋亡事件进行了调查。当人口腔鳞癌细胞系HSC-3暴露于泰索帝72 h时，使用TUNEL法观察到凋亡的剂量依赖性效应。我们观察到半胱天冬酶级联反应的激活，包括半胱天冬酶-3、-8和-9等活性。泛半胱天冬酶抑制剂z-VAD-favorite阻止了泰索帝（0.1 μM）诱导的细胞凋亡，表明半胱天冬酶参与了这一过程。由于拮抗性CD 95-抗体（ZB 4）对泰素特诱导的细胞凋亡没有影响，因此CD 95/CD 95 L相互作用不参与该途径。caspase-8样活性不仅被IETD-fastin（caspase-8）抑制，而且被DEVD-fastin（caspase-3）抑制。结果表明，caspase-8样激活发生在DEVDase下游。泰索帝促进线粒体中活性氧（ROS）的形成，并与抗氧化剂如N-乙酰半胱氨酸和吡咯烷二硫代氨基甲酸酯预孵育细胞，保护细胞免受泰索帝介导的凋亡。此外，泰索帝治疗引起线粒体膜电位降低，细胞色素c释放到胞质溶胶，治疗48小时后。我们观察到泰素帝处理后NF-κB共有位点的结合活性和通过NF-κB干扰线粒体功能。阻断NF-κB的促凋亡作用可抑制紫杉醇诱导的细胞凋亡。因此，这些结果表明，在泰索帝激活NF-κB后，凋亡是通过一种依赖于细胞凋亡的途径引起的

项目成果

Sequence-dependent interaction between cisplatin and histone deacetylase inhibitors in human oral squamous cell carcinoma cells.

• DOI: 10.3892/ijo.28.5.1233
• 发表时间: 2006-05
• 期刊: International journal of oncology
• 影响因子: 5.2
• 作者: Tomonori Sato;Maiko Suzuki;Y. Sato;S. Echigo;H. Rikiishi

Possible role of glutathione in mitochondrial apoptosis of human oral squamous cell carcinoma caused by inorganic selenium compounds.

• DOI: 10.3892/ijo.27.2.489
• 发表时间: 2005-08
• 期刊: International journal of oncology
• 影响因子: 5.2
• 作者: Masato Takahashi;Tomonori Sato;F. Shinohara;S. Echigo;H. Rikiishi

Involvement of NF-κB and mitochondrial pathways in docetaxel-induced apoptosis of human oral squamous cell carcinoma

• DOI: 10.3892/ijmm.15.4.667
• 发表时间: 2005-04
• 期刊: International Journal of Molecular Medicine
• 影响因子: 5.4
• 作者: T. Taniguchi;Masato Takahashi;F. Shinohara;Tomonori Sato;S. Echigo;H. Rikiishi

シスプラチン化学療法における新展開

顺铂化疗新进展

• 发表时间: 2005
• 期刊: 東北大学歯学雑誌 24(1)
• 作者: Higashino F;Aoyagi M;Shindoh M et al.;T.Sato;Karasawa N;T.Sato et al.;Tomonori Sato;Karasawa N;Nakamura H;Kubo K;T.Taniguchi;M.Takahashi;力石秀実
• 通讯作者: 力石秀実

New developments in cisplatin chemotherapy for cancer.

顺铂癌症化疗的新进展。

• 发表时间: 2005
• 期刊: Tohoku University Dental Journal 24(1)
• 作者: Higashino F;Aoyagi M;Shindoh M et al.;T.Sato;Karasawa N;T.Sato et al.;Tomonori Sato;Karasawa N;Nakamura H;Kubo K;T.Taniguchi;M.Takahashi;力石秀実;Kato H;T.Taniguchi et al.;Sasaguri K;M.Takahashi et al.;Karasawa N et al.;SKarasawa N et al.;Nakamura H et al.;Kubo K et al.;H.Rikiishi
• 通讯作者: H.Rikiishi