An antitumor peptide from Musca domestica pupae (MATP) induces apoptosis in HepG2 cells through a JNK-mediated and Akt-mediated NF-kappa B pathway

作者：Zhang, Rongping; Cao, Xiaohong; Wang, Chunling^*; Hou, Lihua; Nie, Jianzeng; Zhou, Minghui; Feng, Yongzhen

来源：Anti-Cancer Drugs, 2012, 23(8): 827-835.

DOI：10.1097/CAD.0b013e32835455f1

• Akt
• antitumor peptide
• apoptosis
• c-Jun N-terminal kinase
• nuclear factor-kappa B

An antitumor peptide from Musca domestica pupae (MATP) was seen to inhibit proliferation and induce apoptosis in cancer cells in our previous investigation. However, the molecular mechanisms involved in MATP-induced apoptosis are still uncharacterized in the human liver cancer cell line HepG2. The present study was undertaken to elucidate the signaling events in MATP-induced apoptosis of HepG2 cells. In this study, the sustained activation of phosphorylated c-Jun N-terminal kinase (JNK) and the obvious inactivation of phosphorylated Akt(Ser473), which prevented I kappa B alpha from degeneration, were induced by MATP. Simultaneously, the apoptosis induced by MATP was reversed by SP600125 (a JNK inhibitor) whereas it was aggravated by LY294002 (an Akt inhibitor). These results proved that JNK and Akt independently participated in the apoptosis of HepG2 cells, which were treated with MATP. Moreover, the activation of phosphorylated JNK together with the inactivation of phosphorylated Akt(Ser473) restrained nuclear factor-kappa B (NF-kappa B p65) from entering the nucleus. The apoptosis induced by MATP was increased by pyrrolidine dithiocarbamate (NF-kappa B p65 inhibitor) and the restriction of NF-kappa B p65 from entering the nucleus induced the decrease of Bcl-2. Simultaneously, MATP induced the increase of Bax, but this mechanism did not depend on the decrease of NF-kappa B p65 in the nucleus. The release of cytochrome c from the mitochondria, which intensified the expression of caspase-9 and caspase-3, was enhanced by the increase in Bax-to-Bcl-2 expression ratio. The apoptosis of HepG2 cells was induced ultimately by the increase in caspase-3. Taken together, these findings suggest that MATP-induced apoptosis through a JNK-mediated and Akt-mediated NF-kappa B pathway.

• 出版日期2012-9
• 单位天津科技大学