Despite recent advances in modern medicine, castration-resistant prostate cancer remains an incurable disease. Subpopulations of prostate cancer cells develop castration-resistance by obtaining the complete steroidogenic ability to synthesize androgens from cholesterol. Statin derivatives, such as simvastatin, inhibit cholesterol biosynthesis and may reduce prostate cancer incidence as well as progression to advanced, metastatic phenotype. In this study, we demonstrate novel simvastatin-related molecules SVA, AM1, and AM2 suppress the tumorigenicity of prostate cancer cell lines including androgen receptor-positive LNCaP C-81 and VCaP as well as androgen receptor-negative PC-3 and DU145. This is achieved through inhibition of cell proliferation, colony formation, and migration as well as induction of S-phase cell-cycle arrest and apoptosis. While the compounds effectively block androgen receptor signaling, their mechanism of inhibition also includes suppression of the AKT pathway, in part, through disruption of the plasma membrane. SVA also possess an added effect on cell growth inhibition when combined with docetaxel. In summary, of the compounds studied, SVA is the most potent inhibitor of prostate cancer cell tumorigenicity, demonstrating its potential as a promising therapeutic agent for castration-resistant prostate cancer.

Infections by the obligate intracellular pathogen Chlamydia trachomatis cause infertility in women of childbearing age. Currently infections caused by the pathogen are treated with antimicrobial therapy. Bacterial ghosts offer a cost-effective, long-term, protective therapy as vaccine delivery vectors. In the present study we tested the hypothesis that factors contained in culture supernatant exhibit anti-chlamydial activity. THP-1 monocytes were differentiated into macrophages (Mdm) by incubating with phorbol myristate acetate (PMA). Activated Mdm were pulsed with Vibrio cholerae ghosts (VCG) for 24 h, followed by the addition of murine splenocytes for an additional 48 h. After 72 h the supernatant was collected and assayed for cytokine concentration. Samples presented observable levels of immunostimulatory factors necessary for containing or clearing infections with chlamydia. Following these assay results, Chlamydia pneumonia (MoPn) elementary bodies (EBs) were suspended in VCG-pulsed THP-1 Mdm supernatant (conditioned media) and used to culture HeLa cells. As a positive control, MoPn was suspended in Earle’s MEM - a medium used for HeLa cell culture. Immunostimulatory factors contained in the conditioned media prevented the development of Chlamydia infection forming units (5.87%) vs. our positive control (94.1%). These results indicate that immunostimulatory factors induced by VCG confer protective immunity against the development cycle of Chlamydia.