Investigation of the Anti-Proliferative and Pro-Apoptotic Effects of Rosemary (Rosmarinus officinalis) Extract on Androgen Independent Prostate Cancer Cells

Abstract

Prostatic carcinoma is established as the third most prevalent cancer type in the worldwide population and accounts for 21% of new cancer cases in Canadian men. Prostate cancer can be categorized as androgen dependent or androgen independent, indicative of the tumor’s ability to respond to testosterone stimulation. Currently available treatments include prostatectomy, radiation therapy, androgen deprivation therapy, immunotherapy, and chemotherapy. Despite all of these treatment options, biochemical reoccurrence, and progression into more advanced stages (castration-resistant prostate cancer- CRPC) is often seen, indicating a need for novel therapeutics that specifically and efficiently target the dysregulated mechanisms in prostate cancer. In some studies, rosemary extract and its polyphenolic constituents have been shown to have anticancer properties, but the exact effects and mechanisms of action are not known. The purpose of the present study was to investigate the potential pro-apoptotic and anti-proliferative effects of rosemary (Rosmarinus officinalis) extract (RE) on prostate cancer cells. PC-3 and 22Rv1 prostate cancer cells, representative in vitro models of androgen independent prostate cancer, as well as the PNT1A non-cancerous prostate epithelial cells were treated with RE and docetaxel (established prostate cancer chemotherapeutic drug) for the purpose of assessing the extent of survival and proliferation, and to investigate changes in expression of key proteins involved in apoptotic and survival signalling cascades. In our studies, RE inhibited the proliferation (IC50: 26 μg/mL; 70 μg/mL) and colony formation efficiency (IC50: 2.8 μg/mL; 4.8 μg/mL) of PC-3 and 22Rv1 prostate cancer cells, respectively, and enhanced cell death by stimulating apoptosis as shown by the increased levels of cleaved caspases 9, 7, 3, and PARP. Enhanced phosphorylation of ERK 1/2, paired with a notable increase in reactive oxygen species (ROS) were also observed in RE- treated PC-3 cells. In contrast, RE had no effect on the proliferation and survival of PNT1A normal epithelial cells, suggesting an action of RE promoting inhibition of prostate cancer cells while sparing non-cancerous epithelial cells.