The flavonol glycoside icariside II (ICA II) has been shown to exhibit a range of anti-tumor properties. Herein, we evaluated the impact of ICA II on human prostate cancer cell proliferation, motility, and autophagy, and we further evaluated the molecular mechanisms underlying these effects. Methods: We treated DU145 human prostate cancer cells with a range of ICA II doses and then assessed their proliferation via CCK-8 assay, while flow cytometry was used to monitor apoptosis and cell cycle progression. We further utilized wound healing and transwell assays to probe the impact of ICA II on migration and invasion, and assessed autophagy via laser confocal fluorescence microscopy. Western blotting was further utilized to measure LC3-II/I, Beclin-1, P70S6K, PI3K, AKT, mTOR, phospho-AKT, phospho-mTOR, and phospho-P70S6K levels, with qRT-PCR being used to evaluate the expression of specific genes at the mRNA level. Results: We found that ICA II was capable of mediating the dose-and time-dependent suppression of DU145 cell proliferation, causing these cells to enter a state of cell cycle arrest and apoptosis. We further determined that ICA II treatment was associated with significant impairment of prostate cancer cell migration and invasion, whereas autophagy was enhanced in treated cells relative to untreated controls. Conclusion: Our results indicate that ICA II treatment is capable of suppressing human prostate tumor cell proliferation and migration while enhancing autophagy via modulating the PI3K-AKT-mTOR signaling pathway. As such, ICA II may be an ideal candidate drug for the treatment of prostate cancer.

Background The flavonol glycoside icariside Ⅱ (ICA II) has been shown to exhibit a range of anti-tumor properties. Herein we evaluated the impact of ICA II on the proliferation, motility, and autophagy activity of human prostate cancer cells, and we further evaluated the molecular mechanisms underlying these effects. Methods Herein, we treated DU145 human prostate cancer cells with a range of ICA II doses. We then evaluated the proliferative abilities of these cells via CCK-8 assay, whereas apoptosis and cell cycle status were assessed via flow cytometry. We further utilized wound healing and transwell assays to probe the impact of ICA II on migratory and invasive activities, while autophagy was assessed via laser confocal fluorescence microscopy. Western blotting was further utilized to measure LC3-II/I, Beclin-1, P70S6K, PI3K, AKT, mTOR, phospho-AKT, phospho-mTOR, and phospho-P70S6K levels, with RT-PCR being used to evaluate the expression of these same genes at the mRNA level. Results We found that ICA II was capable of mediating a dose- and time-dependent suppression of prostate cancer cell proliferative activity, while also causing these cells to enter a state of cell cycle arrest and apoptosis. We further determined that ICA II treatment was associated with significant impairment of prostate cancer cell migratory and invasive abilities, whereas autophagy was enhanced in treated cells relative to untreated controls. Levels of p-P70S6K, p-mTOR, p-AKT, and PI3K were all also decreased by ICA II. Conclusion Our results indicate that ICA II treatment is capable of suppressing human prostate tumor cell proliferation and disrupting migratory activity while enhancing autophagy through PI3K-AKT-mTOR signaling. As such, ICA II may be an ideal candidate drug for the treatment of prostate cancer.