Lee Ji Won, Cho Min Kyung
Department of Pharmacology, College of Oriental Medicine, Dongguk University, Kyungju, 780-714, Korea.
Arch Pharm Res. 2008 Dec;31(12):1604-12. doi: 10.1007/s12272-001-2158-2. Epub 2008 Dec 20.
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.
尽管异硫氰酸盐已被证明可抑制致癌物诱导的肿瘤发生，但尚未有研究确定其治疗乳腺癌的潜力。在本研究中，我们评估了苯乙基异硫氰酸盐（PEITC）对人乳腺癌MCF-7细胞的凋亡活性。暴露于PEITC可有效降低细胞活力。此外，在经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的裂解诱导凋亡，而用半胱天冬酶抑制剂Z-VAD-fmk处理可逆转这些效应。PEITC还导致Bcl-2水平降低，同时Bax水平升高，从而导致细胞色素c的释放。XIAP的抑制和Smac的易位也促成了PEITC诱导的凋亡。然而，PEITC并未增加p53和p21的表达。综上所述，本研究结果表明，PEITC通过线粒体途径显著诱导凋亡。具体而言，PEITC诱导了Bax/Bcl-2比值、XIAP水平和Smac易位的变化，这与细胞色素c的释放以及随后的半胱天冬酶激活相关。因此，PEITC有潜力用作治疗乳腺癌的治疗剂。
