Department of Biochemistry, College of Medicine, Soonchunhyang University, Cheonan 330-090, Republic of Korea.
Int J Mol Med. 2012 Jul;30(1):21-7. doi: 10.3892/ijmm.2012.978. Epub 2012 Apr 23.
Resveratrol (Res), from the skin of red grapes, induces apoptosis in some malignant cells, but there are no reports on the apoptotic effect of Res on human malignant pleural mesothelioma. We found that Res interacts with specificity protein 1 (Sp1). The IC50 for Res was 17 µM in MSTO-211H cells. Cell viability was decreased and apoptotic cell death was increased by Res (0-60 µM). Res increased the Sub-G1 population in MSTO-211H cells and significantly suppressed Sp1 protein levels, but not Sp1 mRNA levels. Res modulated the expression of Sp1 regulatory proteins including p21, p27, cyclin D1, Mcl-1 and survivin in mesothelioma cells. After treatment with Res, apoptosis signaling cascades were activated by the activation of Bid, Bim, caspase-3 and PARP, upregulation of Bax and downregulation of Bcl-xL. Res (20 mg/kg daily for 4 weeks) effectively suppressed tumor growth in vivo in BALB/c athymic (nu+/nu+) mice injected with MSTO-211H cells, an effect that was mediated by inhibition of Sp1 expression and induction of apoptotic cell death. Our results strongly suggest that Sp1 is a novel molecular target of Res in human malignant pleural mesothelioma.
白藜芦醇（Res）来源于红葡萄皮，可诱导一些恶性细胞凋亡，但目前尚无关于 Res 对人恶性胸膜间皮瘤凋亡作用的报道。我们发现 Res 与特异性蛋白 1（Sp1）相互作用。Res 在 MSTO-211H 细胞中的 IC50 为 17µM。Res（0-60µM）可降低细胞活力并增加凋亡细胞死亡。Res 增加了 MSTO-211H 细胞中的 Sub-G1 群体，并显著抑制了 Sp1 蛋白水平，但不影响 Sp1 mRNA 水平。Res 调节了 Sp1 调节蛋白的表达，包括间皮瘤细胞中的 p21、p27、cyclin D1、Mcl-1 和 survivin。用 Res 处理后，凋亡信号级联通过 Bid、Bim、caspase-3 和 PARP 的激活、Bax 的上调和 Bcl-xL 的下调而被激活。Res（20mg/kg，每天一次，持续 4 周）在注射 MSTO-211H 细胞的 BALB/c 无胸腺（nu+/nu+）小鼠体内有效抑制肿瘤生长，这种作用是通过抑制 Sp1 表达和诱导凋亡细胞死亡介导的。我们的研究结果强烈表明 Sp1 是 Res 抑制人恶性胸膜间皮瘤的一个新的分子靶点。
