Genistein Inhibits Human Colorectal Cancer Growth and Suppresses MiR-95, Akt and SGK1

Abstract

Background: Genistein, a major isoflavonoid isolated from dietary soybean, has been shown to suppress the growth of several cancers through modulation of various pathways. However, the molecular mechanisms by which genistein elicit its effects on colorectal cancer (CRC) cells have not been fully elucidated. In this study, we aimed to investigate the anti-tumor activities of genistein on CRC and its potential mechanism. Methods: Effects of genistein on the cell proliferation were tested in HCT-116 cells by MTT assay, and apoptosis was measured by Flow cytometry. Real-time PCR was also used to evaluate the regulation of genistein on miR-95, Akt and SGK1 expression. The protein levels of total Akt (T-Akt), and phosphorylated Akt (P-Akt) were assessed by western blot. A nude mice xenograft model was employed to determine whether genistein could have an anti-tumor effect on CRC in vivo. Results: We found that treatment of HCT-116 cells with genistein caused an inhibition of cell proliferation and induction of apoptosis. Meanwhile, genistein down-regulated the mRNA expression of Akt, SGK1 and miR-95, and inhibited the phosphorylation of Akt in HCT-116 cells. The experiment in vivo also showed that genistein significantly suppressed the growth of mouse xenograft tumor. Conclusion: This study demonstrates that genistein has an inhibitory effect on CRC involved in reducing miR-95, Akt and SGK1, offering novel insights into the mechanisms of genistein therapeutic actions.

Serum and Glucocorticoid Inducible Kinase 1-Sensitive Survival, Proliferation and Migration of Rhabdomyosarcoma Cells

“…Moreover, the sensitivity of RMS cell lines to the cytotoxic drug doxorubicin was enhanced, which is in complete accordance with reports that show SGK1 supporting cell proliferation, stimulating their migration and counteracting apoptosis in diverse tumor cell types [16, 29], including colorectal carcinoma [11-13, 16, 45], hepatocellular carcinoma [17, 18], breast cancer [18-20], prostate cancer [21, 22], glioblastoma [23-25], non-small cell lung cancer [26], meningiomas [27] and medulloblastoma [28]. …”

Cetuximab Enhanced the Cytotoxic Activity of Immune Cells during Treatment of Colorectal Cancer

“…Cetuximab has been approved as first-line treatment of EGFR-positive metastatic CRC and as remedial treatment for other chemotherapy-failed CRC patients [40, 41]. One study showed that cetuximab treatment increased the percentage of NK cells dramatically in vitro [42].…”

Dietary Intervention by Phytochemicals and Their Role in Modulating Coding and Non-Coding Genes in Cancer

“…MiR-1260b was significantly downregulated by genistein in prostate cancer tissues [161]. Qin J. et al, demonstrated that in CRC cells it was observed a significantly reduction of miR-95 levels after genistein treatment [162]. In pancreatic malignancies, genistein determined the induction of apoptosis related with miR-223 inhibition [163].…”