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维生素 C 通过调节内质网钙离子内流和 Bad 与 14-3-3β 的解离诱导人结肠癌细胞系 HCT-8 凋亡。

Vitamin C Induces Apoptosis in Human Colon Cancer Cell Line, HCT-8 Via the Modulation of Calcium Influx in Endoplasmic Reticulum and the Dissociation of Bad from 14-3-3β.

机构信息

Department of Anatomy, Chung-Ang University College of Medicine, Seoul 156-756, Korea.

出版信息

Immune Netw. 2012 Oct;12(5):189-95. doi: 10.4110/in.2012.12.5.189. Epub 2012 Oct 31.

Abstract

It has been reported that vitamin C plays an effective role in the treatment and prevention of cancer, but its specific mechanisms are still largely unknown. The incidence of colon cancer is now increasing in Korea. Therefore, we have examined here the effect of vitamin C on the induction of the apoptosis on colon cancer and its related mechanisms. We have found that remarkable increase of the apoptosis and the calcium influx in endoplasmic reticulum (ER) in human colon cancer cell line, HCT-8. However, vitamin C-induced apoptosis was effectively inhibited by the pre-treatment of BAPTA-AM (1,2-bis(o-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid), which is well-known as a calcium specific chelator. During the apoptosis, we found the increase of the translocation of Bad to mitochondria from cytosol, after releasing from 14-3-3β. In this process, the expression of Bax, a well-known pro-apoptotic protein, was also increased. Taken together, vitamin C induces apoptosis of colon cancer cell line, HCT-8 through the increase of 1) the calcium influx in endoplasmic reticulum (ER), 2) the translocation of Bad to mitochondria, and 3) the expression of Bax.

摘要

据报道,维生素 C 在癌症的治疗和预防中发挥着有效作用,但它的具体机制在很大程度上仍不清楚。目前,韩国结肠癌的发病率正在上升。因此,我们在这里研究了维生素 C 对诱导结肠癌细胞凋亡及其相关机制的影响。我们发现,人结肠癌细胞系 HCT-8 中细胞凋亡和内质网(ER)内钙离子内流显著增加。然而,用 BAPTA-AM(1,2-双(邻氨基苯氧基)乙烷-N,N,N',N'-四乙酸)预处理可有效抑制维生素 C 诱导的细胞凋亡,BAPTA-AM 是一种众所周知的钙特异性螯合剂。在细胞凋亡过程中,我们发现 Bad 从细胞质向线粒体的易位增加,这是在从 14-3-3β 释放之后发生的。在此过程中,众所周知的促凋亡蛋白 Bax 的表达也增加了。综上所述,维生素 C 通过增加 1)内质网(ER)内钙离子内流,2)Bad 向线粒体的易位,3)Bax 的表达,诱导 HCT-8 结肠癌细胞凋亡。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9329/3509163/1699a29997a5/in-12-189-g001.jpg

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