baohuoside-i and Prostatic-Neoplasms

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.. 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.. 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.. 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.

Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Autophagy; Cell Cycle; Cell Line, Tumor; Cell Movement; Cell Proliferation; Dose-Response Relationship, Drug; Flavonoids; Gene Expression Regulation, Neoplastic; Humans; Male; Oncogene Protein v-akt; Phosphatidylinositol 3-Kinases; Prostatic Neoplasms; Signal Transduction; TOR Serine-Threonine Kinases; Wound Healing

Anti-androgens are regarded as potential therapeutic agents for the treatment of prostate cancer. We determined that an epimedium herb (EH) extract exhibited anti-androgenic activity in a luciferase assay using androgen receptor-positive prostate cancer LNCaP cells. Nine EH-derived flavonoids were examined. The results identified icarisid II as a very potent anti-androgenic EH-derived flavonoid. A quantitative RT-PCR analysis confirmed that the flavonol suppressed the expression of the androgen-responsive KLK3 gene.

Topics: Androgen Antagonists; Androgens; Cell Line, Tumor; Drugs, Chinese Herbal; Epimedium; Flavonoids; Gene Expression; Humans; Kallikreins; Male; Phytotherapy; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Receptors, Androgen

Icariside II (IS) isolated from the roots of Epimedium koreanum Nakai was known to have antioxidant activity and inhibit melanogenesis and hypoxia inducible factor. We report here for the first time that IS induces apoptosis through its anti-inflammatory effects in PC-3 prostate cancer cells. IS exerted cytotoxicity against PC-3 cells with IC(50) of approximately 20 microM. IS suppressed both constitutive and arachidonic acid (AA)-induced cyclooxygenase-2 (COX-2) expression as well as reduced prostaglandin E2 (PGE2) levels in PC-3 cells even at a low concentrations (5 and 10 microM). Additionally, IS increased sub G1 apoptotic portion and exhibited terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL)-positive apoptotic bodies in PC-3 cells at higher concentrations (20 and 40 microM). Furthermore, IS attenuated the mitochondrial membrane potential, released cytochrome C into cytosol, activated caspase-9, -8, and -3 expressions and cleaved poly (ADP-ribose) polymerase (PARP) in PC-3 cells. Consistently, COX-2, inducible NO synthase (iNOS), and vascular endothelial growth factor (VEGF) expressions were suppressed while in parallel inducing apoptosis in hormone-independent prostate carcinoma cells PC-3. Moreover, exogeneous PGE2 inhibited IS induced PARP cleavage in PC-3 cells and also knockdown of COX-2 by siRNA potentiated IS induced PARP cleavage, thereby implicating the critical role of COX-2 pathway in IS induced apoptosis. Taken together, these findings demonstrate that IS initiates the inhibition of COX-2/PGE(2) pathway and then induces apoptosis mainly via mitochondrial dependent pathway in PC-3 prostate cancer cells as a potent cancer chemotherapeutic agent.

Topics: Antineoplastic Agents; Apoptosis; Caspase 3; Caspase 8; Caspase 9; Cell Line, Tumor; Cyclooxygenase 2; Flavonoids; Humans; Inhibitory Concentration 50; Male; Nitric Oxide Synthase Type II; Poly(ADP-ribose) Polymerases; Prostatic Neoplasms; Vascular Endothelial Growth Factor A