Alphitolic acid, an anti-inflammatory triterpene, induces apoptosis and autophagy in oral squamous cell carcinoma cells, in part, through a p53-dependent pathway

作者：Bai Li Yuan; Chiu Chang Fang; Chiu Shih Jiuan; Chen Yu Wen; Hu Jing Lan; Wu Chia Yung; Weng Jing Ru^*

来源：Journal of Functional Foods, 2015, 18: 368-378.

DOI：10.1016/j.jff.2015.07.017

• Alphitolic acid
• Oral squamous cell carcinoma
• Apoptosis
• Autophagy
• p53

The antitumour mechanism of alphitolic acid (ALA), an anti-inflammatory triterpene, in oral squamous cell carcinoma (OSCC) cells was investigated. ALA suppressed the proliferation of SCC4 and SCC2095 OSCC cells with IC50 values of 12 and 15 mu M, respectively, via apoptotic induction. Mechanistically, this drug effect on apoptosis was, in part, associated with its ability to block Akt-NF-kappa B signalling. Moreover, ALA induced autophagy, as evidenced by increased expression of the autophagy biomarkers Beclin 1, Atg7, and LC3B-II, and autophagosome formation. This autophagy induction played a protective role as autophagy inhibitors enhanced cellular susceptibility to ALA-induced apoptosis. Also noteworthy is the involvement of p53 in ALA-mediated cytotoxicity. ALA increased p53 phosphorylation/expression, accompanied by parallel decreases in the expression of the oncogenic E3 ligase MDM2, and shRNA-mediated knockdown of p53 partially rescued ALA-mediated cytotoxicity. Together, these findings suggest the translational value of ALA as an ingredient in functional food/dietary supplement for OSCC prevention.

• 出版日期2015-10
• 单位中国医科大学