Prostate cancer (PCa) is the top male diagnosed cancer in the United States. The androgen receptor (AR) controls the functions of androgens within the prostate and is a major factor in PCa development. A strong correlation between cancer and inflammation has been shown. Inflammation creates a microenvironment that is favorable to the development and progression of cancer. Natural cucurbitacins are recognized as a result of their anti-inflammatory, anti-cancer and hepatoprotective properties. The multi-faceted binding of the cucurbitacins make them potential drug candidates to treat prostate cancer.
Several estrone and cucurbitane analogs have been identified through molecular modeling to target the androgen receptor and therefore may be applicable in the treatment of prostate cancer. In vitro and in vivo results showed several analogs performing better than the standard nilutamide. Further evidence of androgen receptor binding has been generated through an androgen receptor competitive assay. Several estrone and cucurbitacin analogs showed stronger or similar binding to the AR than nilutamide.
The potential of cucurbitacins and their analogs as lead drug candidates for the treatment of prostate cancer. The compounds developed have the potential to reduce cancer resistance through stronger androgen receptor binding as well as perform better than the current treatments in the marketplace and lower hepatotoxicity. Cucurbitacins have more potential as multifaceted drugs as they reduce inflammation due to carcinogenicity and play an important role in controlling Hsp90.