ProstaCaid Induces G2/M Cell Cycle Arrest and Apoptosis in Human and Mouse Androgen-Dependent and-Independent Prostate Cancer Cells

Abstract

The anticancer effects of ProstaCaid, a novel integrative blend of vitamins, minerals, multiherb extracts, and derivatives, were tested in human and mouse androgen—dependent (AD) and —independent (AI) prostate cancer cell lines. ProstaCaid shows growth inhibitory effects on both human and mouse AD prostate cancer cells (LNCaP and CASP 2.1) and AI prostate cancer cells (PC3 and CASP 1.1) in a dose-/time-dependent manner. Consistently, long-term treatment with ProstaCaid also reduced colony formation capacities of prostate cancer cells. Flow cytometry assays revealed that ProstaCaid induces G2/M arrest and apoptosis in LNCaP and PC3 cells after 72 hours of treatment. Immunoblotting assay demonstrated that 25 µg/mL of ProstaCaid treatment resulted in (1) the reduction of cyclin D1, cyclin B1, and Cdc2 expression in a time-dependent way; (2) increase in p21^WAF1/Cip1 as early as 12 hours after the treatments in PC3 cells and reduction to base line at the 72-hour time point; and (3) repression of Bcl-2, BclxL, and induction of Bim as well as the cleavages of caspase-3 and poly(ADP-ribose) polymerase (PARP) at 72 hours of treatment, suggesting caspase-3-dependent apoptosis. Moreover, ProstaCaid suppressed activation of AKT and MAPK signaling pathways in PC3 and LNCaP cells by reducing phosphorylation levels of AKT, its downstream target S6 ribosomal protein and GSK3β, and ERK1/2, respectively. In summary, these findings strongly suggest that ProstaCaid may be a potential chemopreventive and therapeutic agent for both AD and, more importantly, AI prostate cancer.

Keywords

prostate cancer herbal medicine cell cycle arrest apoptosis AKT signal pathway MAPK signal pathway

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