Department of Marine Life Sciences, Jeju National University, Republic of Korea.
Cancer Lett. 2010 Sep 28;295(2):260-6. doi: 10.1016/j.canlet.2010.03.009. Epub 2010 May 6.
Sulforaphane (SFN), a dietary isothiocyanate, is a well known natural product that possesses anti-cancer and chemopreventive activities. However, the molecular mechanism of the anti-telomerase activity of SFN is not well understood. In this study, we investigated the hypothesis that SFN inhibits cell viability and telomerase activity via downregulation of telomerase reverse transcriptase (hTERT) expression. We suggest that elevated intracellular reactive oxygen species (ROS) levels, due to exposure to SFN, has a critical role in abolishing since pretreatment with NAC, an antioxidant, resulted in the recovery of hTERT expression. SFN also suppressed the phosphorylation of Akt (Ser-473), thereby inhibiting hTERT phosphorylation and this effect was reversed by pretreatment with NAC. Taken together, these data suggest that ROS are essential for the suppression of SFN-mediated telomerase activity via transcriptional and posttranslational regulation of hTERT.
萝卜硫素（SFN），一种饮食中的异硫氰酸盐，是一种众所周知的具有抗癌和化学预防作用的天然产物。然而，SFN 抑制端粒酶活性的分子机制尚不清楚。在这项研究中，我们假设 SFN 通过下调端粒酶逆转录酶（hTERT）表达来抑制细胞活力和端粒酶活性。我们认为，由于暴露于 SFN 而导致的细胞内活性氧（ROS）水平升高在消除端粒酶活性中起着关键作用，因为用抗氧化剂 NAC 预处理会导致 hTERT 表达恢复。SFN 还抑制 Akt（Ser-473）的磷酸化，从而抑制 hTERT 的磷酸化，而用 NAC 预处理可逆转这种作用。总之，这些数据表明，ROS 对于通过 hTERT 的转录和翻译后调控抑制 SFN 介导的端粒酶活性是必不可少的。
