Zhang Xiali, Tu Shuo, Wang Yibing, Xu Baohua, Wan Fusheng
Department of Laboratory Animal Science, Nanchang University, Nanchang 330006, China.
Acta Biochim Biophys Sin (Shanghai). 2014 Apr;46(4):261-72. doi: 10.1093/abbs/gmu004. Epub 2014 Mar 7.
Taurine (Tau) has been shown to possess cancer therapeutic effect through induction of apoptosis, while the underlying molecular mechanism of its anti-cancer effect is not well understood. PUMA (p53-upregulated modulator of apoptosis) plays an important role in the process of apoptosis induction in a variety of human tumor cells in both p53-dependent and -independent manners. However, whether PUMA is involved in the process of Tau-induced apoptosis in cancer cells has not been well studied. In the present study, we treated human colorectal cancer cells HT-29 (mutant p53) and LoVo (wild-type p53) with different concentrations of Tau, which led to the repression of cell proliferation and induction of apoptosis in both cell lines. Meanwhile, we also observed the increased expression of PUMA and high Bax/Bcl-2 ratios. To determine the role of PUMA in Tau-induced apoptosis, we used small interfering RNA interference to suppress PUMA expression. As a result, apoptosis was decreased in response to Tau treatment. All these results indicated that PUMA plays a critical role in Tau-induced apoptosis pathway in human colorectal cancer cells. Demonstration of the molecular mechanism involved in the anti-tumor effect of Tau may be useful in the therapeutic target selection for p53-deficient colorectal cancer.
牛磺酸(Tau)已被证明可通过诱导细胞凋亡发挥癌症治疗作用,但其抗癌作用的潜在分子机制尚不清楚。p53上调凋亡调节因子(PUMA)在多种人类肿瘤细胞的凋亡诱导过程中,以p53依赖性和非依赖性方式发挥重要作用。然而,PUMA是否参与癌细胞中Tau诱导的凋亡过程尚未得到充分研究。在本研究中,我们用不同浓度的Tau处理人结肠癌细胞HT-29(p53突变体)和LoVo(p53野生型),这导致两种细胞系的细胞增殖受到抑制并诱导细胞凋亡。同时,我们还观察到PUMA表达增加以及Bax/Bcl-2比值升高。为了确定PUMA在Tau诱导的凋亡中的作用,我们使用小干扰RNA干扰来抑制PUMA表达。结果,Tau处理后细胞凋亡减少。所有这些结果表明,PUMA在人结肠癌细胞中Tau诱导的凋亡途径中起关键作用。阐明Tau抗肿瘤作用的分子机制可能有助于p53缺陷型结肠癌的治疗靶点选择。