<p>The Impact of Icariside II on Human Prostate Cancer Cell Proliferation, Mobility, and Autophagy via PI3K-AKT-mTOR Signaling Pathway</p>

Abstract

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.

Icariside II: Anticancer Potential and Molecular Targets in Solid Cancers

“…In human esophageal squamous carcinoma Eca109 cells, Icariside II was demonstrated to be highly effective in downregulating β-catenin and cyclin D1 protein expression and stochastically inducing cell cycle arrest (Wang et al, 2011). The cell cycle blockage in human PC-3 and DU145 prostate cancer cells at the G0/G1 checkpoint was caused by Icariside II in a dose-dependent manner, which increased the percentage of cells undergoing G1 phase cell cycle arrest to 45.7-80% upon treatment with 40 µM (Lee et al, 2009;Li et al, 2020). These results were supported in a study by Wei Z, which showed that Icariside II induced significant accumulation of cells at the G1/G0 phase with decreased cell populations at the S phase and the G2/M phase in cervical cancer (Sun et al, 2020).…”

“…Icariside II, as a novel phosphodiesterase 5 inhibitor, was found to play a role in regulating autophagy via the PI3K/AKT/ mTOR, ROS/GSK-3β/mitochondrial, and PKG/GSK-3β signaling pathways in different diseases (Gao et al, 2017;Gao et al, 2020;Li et al, 2020;Zhang et al, 2020). In human prostate cancer, autophagy induced by Icariside II was characterized by enhanced autophagosome formation, reduction in P70S6K expression, and upregulation of LC3 and Beclin-1 by inhibiting PI3K-AKT-mTOR activity (Li et al, 2020). Till date, the influence of Icariside II on autophagy in different cancer cell lines is not well elucidated and more studies are needed to shed better light on this subject.…”

“…Accumulating evidence is indicating that Icariside II has the ability to control cancer cell invasion and migration in lung cancer (Song et al, 2017), hepatocellular carcinoma (Guo et al, 2020a), cervical cancer (Sun et al, 2020b), osteosarcoma (Choi et al, 2008), melanoma (Peng and Zhang, 2018), and prostate cancer (Li et al, 2020). In hepatocellular carcinoma (Guo et al, 2020b) and cervical cancer (Sun et al, 2020a), it has been demonstrated that Icariside II could weaken the migratory and invasive ability of HuH-7, HepG2, and HeLa cells through inhibiting metastasis-related protein MMP2/9 expression.…”

Astragalus–Scorpion Drug Pair Inhibits the Development of Prostate Cancer by Regulating GDPD4-2/PI3K/AKT/mTOR Pathway and Autophagy

“…In addition, the TCM, Jixuepaidu Tang-1, and Astragaloside IV have also been confirmed to be involved in the process of liver cancer and kidney injury by regulating ATB ( Li et al, 2018 ) and LOC498759 ( Jin et al, 2019 ), respectively. It was known that the treatment of flavanol glycoside icaridin, the active ingredient of TCM, could inhibit the proliferation and migration of human PCa cells and enhance autophagy by regulating the PI3K/AKT/mTOR signaling pathway ( Li S. et al, 2020 ). However, the effects of the A–S drug pair on the PI3K pathway, autophagy, and lncRNAs have never been studied in PCa.…”

Pharmacological mechanism and therapeutic efficacy of Icariside II in the treatment of acute ischemic stroke: a systematic review and network pharmacological analysis

“…Herba Epimedii (commonly named as Yin-yang-huo in China) is a traditional herb or health food that is widely used in China for the prevention and treatment of various diseases. In vivo and in vitro studies have been conducted over the past few decades and found that ICS II can treat a variety of cancers including acute myeloid leukemia [ 15 ], prostate cancer [ 16 ], cervical cancer [ 17 ], etc. It has also been used to treat myocardial ischemic and reperfusion injury [ 18 , 19 ], ED [ 20 , 21 ] and many neurological disorders such as Alzheimer's disease [ 22 – 24 ], vascular dementia [ 25 ], and subarachnoid hemorrhage [ 26 ].…”