Inhibitory Effect of Jatrorrhizine-Platinum(II) Complex on Prostate Cancer Cells via PI3K/AKT and STA3/JAK2 Phosphorylation Downregulation

Abstract

Background: Prostate cancer is common in men worldwide and its incidence in China has increased over the last 2 decades. The present study assessed the cytotoxicity of jatrorrhizine-platinum(II) complex [JR-P(II)] against prostate cancer and investigated the associated mechanism. Material/Methods: MTT assay was used to assess the anti-proliferative potential and flow cytometry was used to assess apoptosis induction ability of JR-P(II). The protein expression was determined using Western blot assay. JR-P(II)induced changes in Akt mRNA were assessed by RT-PCR assay and MMP was evaluated by flow cytometry using Rhodamine 123 staining. Results: JR-P(II) inhibited 22Rv1 cell and LNCaP cell viability by 17% and 24%, respectively, after treatment with 16 μM JR-P(II). In JR-P(II)-treated 22Rv1 cells and LNCaP cells, the levels of cleaved-PARP and caspase-3 were elevated by 4.0, 8.0, and 16 μM JR-P(II). JR-P(II) treatment increased 22Rv1 and LNCaP cell populations in S phase, with reduction of G1/G0 and G2/M phase cell count. Treatment of 22Rv1 and LNCaP cells with JR-P(II) caused reduction of cyclin E1/A1/D1, pRb, and E2F1 proteins. Moreover, JR-P(II) treatment elevated p53 expression in 22Rv1 and LNCaP cells. JR-P(II) treatment raised ROS level and suppressed MMP in 22Rv1 and LNCaP cells. JRP(II) treatment increased cytochrome c and Bax expression, and reduced Bcl-2 expression in 22Rv1 and LNCaP cells. In JR-P(II)-treated 22Rv1 and LNCaP cells, PI3K/Akt/ERK activation was downregulated relative to the control group. JAK2 and STAT3 phosphorylation gradually decreased with increased JR-P(II) concentration, from 4.0 to 16 μM. Conclusions: JR-P(II) inhibits prostate cancer cell proliferative potential via oxidative damage-induced apoptosis, and it downregulated PI3K/AKT and STA3/JAK2 pathway activation in prostate cancer cells. Therefore, JR-P(II) shows promise for use in treatment of prostate cancer.