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苯乙基异硫氰酸酯(PEITC)通过 G0/G1 期阻滞和线粒体介导的凋亡性细胞死亡抑制人口腔鳞状细胞癌细胞 HSC-3 的生长。

Phenethyl Isothiocyanate (PEITC) Inhibits the Growth of Human Oral Squamous Carcinoma HSC-3 Cells through G(0)/G(1) Phase Arrest and Mitochondria-Mediated Apoptotic Cell Death.

机构信息

Department of Biological Science and Technology, China Medical University, Taichung 40402, Taiwan.

出版信息

Evid Based Complement Alternat Med. 2012;2012:718320. doi: 10.1155/2012/718320. Epub 2012 Jul 10.

Abstract

Phenethyl isothiocyanate (PEITC), an effective anticancer and chemopreventive agent, has been reported to inhibit cancer cell growth through cell-cycle arrest and induction of apoptotic events in various human cancer cells models. However, whether PEITC inhibits human oral squamous cell carcinoma HSC-3 cell growth and its underlying mechanisms is still not well elucidated. In the present study, we evaluated the inhibitory effects of PEITC in HSC-3 cells and examined PEITC-modulated cell-cycle arrest and apoptosis. The contrast-phase and flow cytometric assays were used for examining cell morphological changes and viability, respectively. The changes of cell-cycle and apoptosis-associated protein levels were determined utilizing Western blotting in HSC-3 cells after exposure to PEITC. Our results indicated that PEITC effectively inhibited the HSC-3 cells' growth and caused apoptosis. PEITC induced G(0)/G(1) phase arrest through the effects of associated protein such as p53, p21, p17, CDK2 and cyclin E, and it triggered apoptosis through promotion of Bax and Bid expression and reduction of Bcl-2, leading to decrease the levels of mitochondrial membrane potential (ΔΨ(m)), and followed the releases of cytochrome c, AIF and Endo G then for causing apoptosis in HSC-3 cells. These results suggest that PEITC could be an antitumor compound for oral cancer therapy.

摘要

苯乙基异硫氰酸酯(PEITC)是一种有效的抗癌和化学预防剂,已被报道通过细胞周期阻滞和诱导各种人类癌细胞模型中的凋亡事件来抑制癌细胞生长。然而,PEITC 是否抑制人口腔鳞状细胞癌 HSC-3 细胞的生长及其潜在机制尚不清楚。在本研究中,我们评估了 PEITC 在 HSC-3 细胞中的抑制作用,并研究了 PEITC 调节的细胞周期阻滞和凋亡。相差和流式细胞术分别用于检查细胞形态变化和活力。在用 PEITC 处理 HSC-3 细胞后,利用 Western blot 测定细胞周期和凋亡相关蛋白水平的变化。我们的结果表明,PEITC 能有效抑制 HSC-3 细胞的生长并诱导细胞凋亡。PEITC 通过相关蛋白如 p53、p21、p17、CDK2 和 cyclin E 的作用诱导 G0/G1 期阻滞,并通过促进 Bax 和 Bid 的表达和降低 Bcl-2 的水平来触发凋亡,导致线粒体膜电位(ΔΨ(m))降低,随后细胞色素 c、AIF 和 Endo G 的释放导致 HSC-3 细胞凋亡。这些结果表明,PEITC 可能是口腔癌治疗的一种抗肿瘤化合物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52de/3418800/6aa67cecbfa3/ECAM2012-718320.001.jpg

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