Phenethyl isothiocyanate induced apoptosis via down regulation of Bcl-2/XIAP and triggering of the mitochondrial pathway in MCF-7 cells
Phenethyl isothiocyanate induced apoptosis via down regulation of Bcl-2/XIAP and triggering of the mitochondrial pathway in MCF-7 cells
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DOI：
10.1007/s12272-001-2158-2
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发表时间：
2008-12-01
影响因子：
6.7
通讯作者：
Cho, Min Kyung
中科院分区：
文献类型：
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作者：
Lee, Ji Won;Cho, Min Kyung
虽然异硫氰酸酯已被证明可以抑制致癌物诱导的肿瘤发生，但尚未进行研究以确定其治疗乳腺癌的治疗潜力。在本研究中，我们评估了苯乙基异硫氰酸酯（PEITC）在人乳腺癌MCF-7细胞中的凋亡活性。暴露于PEITC有效地降低了细胞活力。此外，在PEITC处理的细胞中检测到DNA片段和TUNEL阳性细胞核。此外，PEITC通过激活半胱天冬酶7和9以及PARP的裂解诱导细胞凋亡，并且这些作用通过用半胱天冬酶抑制剂Z-VAD-fetamine处理而逆转。PEITC还引起Bcl-2水平的降低，伴随Bax水平的增加，这导致细胞色素c的释放。XIAP抑制和Smac易位也有助于PEITC诱导的细胞凋亡。PEITC对p53和p21的表达无明显影响。总之，本研究的结果表明，PEITC通过线粒体途径显著诱导细胞凋亡。具体而言，PEITC诱导Bax/Bcl-2比率、XIAP水平和Smac易位的变化，其与细胞色素c的释放和随后的半胱天冬酶活化相结合。因此，PEITC具有用作治疗乳腺癌的治疗剂的潜力。
Although isothiocyanates have been shown to inhibit carcinogen-induced tumorigenesis, no studies have been made to determine their therapeutic potential for the treatment of breast cancer. In the present study, we evaluated the apoptotic activities of phenethyl isothiocyanate (PEITC) in human breast cancer MCF-7 cells. Exposure to PEITC potently reduced cell viability. In addition, DNA fragments and TUNEL positive nuclei were detected in PEITC-treated cells. Furthermore, PEITC induced apoptosis via activation of caspases 7 and 9 and the cleavage of PARP, and these effects were reversed by treatment with the caspase inhibitor, Z-VAD-fmk. PEITC also caused a decrease in the levels of Bcl-2 with a concomitant increase in Bax levels, which resulted in the release of cytochrome c. XIAP suppression and Smac translocation also contributed to the PEITC-induced apoptosis. However, PEITC did not increase the expressions of p53 and p21. Taken together, the results of this study demonstrate that PEITC significantly induces apoptosis via a mitochondrial pathway. Specifically, PEITC induced a change in the Bax/Bcl-2 ratios, XIAP levels and Smac translocation that was conjunction with the release of cytochrome c and following caspase activation. Therefore, PEITC has the potential for use as a therapeutic agent for the treatment of breast cancer.