Abstract 3290: Modulation of AKT, ERK and Mcl-1 by apigenin sensitizes colon cancer cells to anti-tumor activities of ABT263.

Abstract

Apigenin is an edible plant-derived flavonoid showing anti-tumor activities in vitro and in vivo. Pretreatment with apigenin resulted in cell growth arrest and/or apoptosis in various types of tumors via modulating multiple cell signaling pathways. In the present study, we evaluated interactions between apigenin and ABT263 in multiple colon cancer cell lines. We found that apigenin enhanced ABT263-induced apoptosis in colon cancer cells in a time- and dose-dependent manner. ABT263 alone only resulted in limited cell killing in association with upregulation of Mcl-1, a potential mechanism for acquired ABT263 resistance. Apigenin antagonized ABT263-induced Mcl-1 expression and dramatically enhanced ABT263-induced cell death. Apigenin also suppressed AKT and ERK activation. Inactivation of either AKT or ERK pathway by lentivirus-transduced shRNA or specific small molecule inhibitors synergized with ABT263 to induce cell death, reflecting that AKT and ERK pathways are apigenin targets. Moreover, the synergism between ABT263 and apigenin was associated with the upregulation of Bim and subsequent activation of Bax. Xenograft studies with HCT116 cells in SCID mice showed that the combination treatment with apigenin and ABT263 inhibited tumor growth up to 70% without obvious adverse effects, while either agent alone showed only about 30% inhibition. Collectively, our findings demonstrate a novel and effective strategy to treat colon cancer by combination of ABT263 and apigenin. The combined effect is mediated by apigenin downregulation of Mcl-1, Akt and ERK activities. Citation Format: Huanjie Shao, Kai Jing, Esraa Mahmoud, Xianjun Fang, Chunrong Yu. Modulation of AKT, ERK and Mcl-1 by apigenin sensitizes colon cancer cells to anti-tumor activities of ABT263. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3290. doi:10.1158/1538-7445.AM2013-3290

Manuka honey enhanced sensitivity of HepG2, hepatocellular carcinoma cells, for Doxorubicin and induced apoptosis through inhibition of Wnt/β-catenin and ERK1/2

“…Furthermore, Ding et al demonstrated that quercetin reduced cell viability, induced apoptosis, cleaved caspase-3, cleaved PARP, upregulated Bax protein expression, and downregulated p-ERK1/2 protein levels in HepG2 cells [ 57 ]. Shao et al demonstrated that phytochemicals, such as apigenin (one of the flavonoids present in MH), downregulates the activation of ERK and Akt in human colon cancer cells [ 58 ]. Moreover, ERK1/2 has been previously implicated with β-catenin, mTOR, and cyclin D1 in cellular proliferation [ 39 , 59 ].…”