Anti-cancer bioactive peptide induces apoptosis in gastric cancer cells through TP53 signaling cascade

Our previous studies show that anti-cancer bioactive peptide (ACBP) inhibits the initiation and progression of gastric cancer via apoptosis and cell cycle arrest, however, the mechanisms is not clear. Here, we studied the effects of ACBP in three human gastric cancer cell lines, NCI-N87 and MGC-803, and investigated effect of ACBP on the survival and morphology of the cancer cell lines, examined apoptosis and cell cycle progression, detected the expression of TP53, TP63, and TP73 in cancer cells and the expression of Bax, PUMA and Mcl-1 in xenograft mouse model. ACBP inhibited the proliferation of three cancer cells dose-dependently as did the positive control and 5-fluorouracil (5-Fu). The effect of ACBP correlated with the degree of differentiation of cancer cells, the lower the differentiation degree, the stronger the inhibitory effect. After ACBP treatment, TP53, TP63 and TP73 expression was increased in all cell lines. In xenogragft mouse model, ACBP inhibited growth of MGC-803 cell in vivo. Apoptotic related genes Bax and PUMA were up-regulated, and Mcl-1 was down-regulated. ACBP inhibited tumor cell growth by induced apoptosis through TP53 signaling cascade by up-regulating TP53, TP63 and TP73 and its downstream apoptosis promoting genes Bax and PUMA, down-regulating antiapoptotic gene Mcl-1.