Genistein induces activation of the mitochondrial apoptosis pathway by inhibiting phosphorylation of Akt in colorectal cancer cells

Abstract

Context: Genistein inhibits the proliferation and induces apoptosis of colorectal cancer cells; however, the underling molecular mechanisms remain to be determined. Aim: The aim of this study was to investigate whether genistein reduces cell viability by suppressing the phosphorylation of AKT and activating the mitochondrial apoptosis pathway in colorectal cancer cells. Materials and methods: The anti-proliferative effects of genistein (0, 25, 50, and 100 mM) on HCT-116 and LoVo cells were assessed using MTT assay. Genistein-induced apoptosis was measured by Hoechst 33258 staining and flow cytometry. The mRNA level of Bax was detected by real-time PCR. The protein levels of Bax, total Akt, and phosphorylated Akt were assessed by western blot. Results: The IC 50 values of genistein were 690, 135, and 61 mM in HCT-116 cells and 204, 135, and 93 mM in LoVo cells after treatment for 24, 48, and 72 h, respectively. After treatment with different concentrations of genistein (0, 25, 50, and 100 mM) for 48 h, the early apoptotic cells in HCT-116 increased from 1.99% ± 0.55% to 6.78% ± 2.12%, 23.16% ± 3.87%, and 36.99% ± 3.76%, respectively. The same concentrations of genistein increased the early apoptotic cells in LoVo from 2.56% ± 1.42% to 3.21% ± 1.52%, 18.22% ± 3.56%, and 23.56% ± 3.02%, respectively. Moreover, genistein increased the mRNA and protein levels of Bax, while it inhibited the phosphorylation of Akt in HCT-116 cells. Conclusion: Genistein inhibited cell proliferation and induced apoptosis of colorectal cancer cells. Genistein induced the mitochondrial pathway of apoptosis in HCT-116 cells by inhibiting phosphorylation of Akt.

Genistein inhibits the growth and regulates the migration and invasion abilities of melanoma cells via the FAK/paxillin and MAPK pathways

“…Furthermore, genistein induced its apoptotic effect in a dose-dependent manner. This observation is in agreement with the cytotoxic properties of genistein reported in other studies using different cell types [40, 43, 44]. …”

Genistein reduces the activation of AKT and EGFR, and the production of IL6 in cholangiocarcinoma cells involving estrogen and estrogen receptors

“…AKT protein is a promising target for CCA treatment as its expression and activation increase during the development and progression of CCA (5-7). Studies in colorectal cancer cells have demonstrated that GE can induce apoptosis by inhibiting the activation of AKT (30). Therefore, the present study examined whether GE attenuated the activity of AKT in the CCA cell lines.…”

Flavonoids as Anticancer Agents

“…Isoflavonoid genistein could regulate estrogen receptor-α expression and change Bax/Bcl-2 ratio downregulating proliferation, differentiation, and activating apoptosis in MCF-7 and 3T3-L1 cells [93]. Moreover, genistein suppressed Bcl-2, Bcl-xL, c-inhibitor of apoptosis protein 1 (c-IAP1), survivin, and NF-κB in C200 and A2780 cells [94], increased caspase-3 activity in HT-29 colon cancer cells [95] and activated intrinsic apoptotic signaling pathway in HCT-116 and LoVo cells [96]. Isoflavonoid daidzein also acted as phytoestrogen [97].…”