Study on the Mechanism of Diosgenin Targeting STAT3 to Inhibit Colon Cancer Proliferation and Migration

Abstract

To elucidate regulatory effects and molecular mechanisms of diosgenin on colon cancer, this study administered diosgenin at concentrations of 10 (low), 50 (medium), and 100 μmol/L (high concentration group) at the cell level, respectively. EdU, colony formation, and Transwell assays were implemented to determine SW480 cellular proliferation and migration. Assays of flow cytometry and TUNEL were employed to estimate cell apoptosis. Additionally, nude mouse tumorigenesis assay was used to further verify the regulatory function of diosgenin on colon cancer. The target protein of diosgenin was predicted via molecular docking. The results showed that all three concentrations of diosgenin could reduce colon cancer cellular proliferation and migration, and after diosgenin treatment, colon cancer cellular apoptosis was markedly increased, and the 100 μmol/L diosgenin group produced the most satisfactory inhibition on colon cancer cell proliferation. Ki67 expression was markedly reduced whereas those of Bax and caspase3 were greatly increased after diosgenin treatment. The nude mouse tumorigenesis assay indicated that the parameters of tumorous volume and mass of diosgenin treatment group were greatly decreased as compared to control, and as the concentration of diosgenin increased, the inhibitory effect was more significant. Molecular docking indicated that STAT3 served as a target protein of diosgenin. Moreover, after diosgenin treatment on colon cancer cells, the STAT3 expression was markedly reduced. The STAT3 overexpression would counteract the inhibitory effect of 50 μmol/L diosgenin in both suppressing colon cancer cellular proliferation and migration and promoting apoptosis. Taken together, all our outcomes demonstrated the diosgenin effects in not only inhibiting colon cancer cellular proliferation and migration but also promoting cancerous cellular apoptosis. Diosgenin is a regulatory player in targeting and regulating STAT3.

Steroidal Saponins: Naturally Occurring Compounds as Inhibitors of the Hallmarks of Cancer

“…cell proliferation in a dose-dependent manner and exceeded the inhibitory effects o reference drug cisplatin. These results were further verified in a colon cancer nude m model [32]. Similarly, diosgenin downregulated the activation of the NF-κB/STAT3 p way in the transgenic prostate cancer mouse model by preventing the phosphorylatio IKK and subsequently reducing IκBα and p65 phosphorylation [33].…”

“…Dioscin and diosgenin seem to be the most promising steroidal saponins due to their multifaceted anti-cancer activities that target most hallmarks of cancer. Both compounds surpassed the anti-cancer effectiveness of established reference drugs, such as adriamycin and cisplatin [32,90]. However, it has been reported that dioscin and diosgenin possess poor bioavailability, impeding their clinical development [91,92].…”

Case Report: Colon malignant tumor caused by retroperitoneal small round cell undifferentiated sarcoma

“…Currently, research on the molecular mechanism and treatment focus of colon malignant tumors has reached a relatively mature stage (4). This includes exploring microsatellite instability, CpG island hypermethylation, and various gene mutations associated with carcinogenesis (5,6). However, the correlation between small round cell undifferentiated sarcoma and malignant colon tumors remains unclear, and further investigation is needed to explore any related molecular mechanisms.…”

Effect of Kaempferol on the Biological Behavior of Human Colon Cancer via Regulating MMP1, MMP2, and MMP9

“…Following that, a serum-freedrug-containing medium was added for continued incubation. Finally, images were collected at the appropriate time using a Nikon TS2-S-SM inverted microscope and then processed using ImageJ software (version 8.0, Madison, WI, USA) to calculate the proportion of cell-free area in the treated group versus the control groups [ 16 , 17 ].…”

“…Following washing with PBS, the upper-layer cells that did not migrate were wiped off with a damp cotton swab, and the chamber was then air-dried. Finally, an inverted microscope was used to observe cell migration [ 17 ].…”