Growth Hormone Releasing Hormone Receptors Antagonists and Cancers: Do GHRH-R Antagonists Play a Role in the Management of Prostate Cancer?

Growth hormone-releasing hormone (GHRH) and its receptors have been implicated in the progression of various tumors such as those of the prostate. Treatment modalities for prostate cancer in a localized stage or when it is still castration-sensitive yield good results in most patients. However, such treatments are only palliative in the advanced stage. Therefore, new therapeutic targets like growth hormone-releasing hormone receptor (GHRH-R) and its splice variants should be found in order to get effective treatments for more aggressive stages in prostate cancer. This review talks about the GHRH-R and its splice variants, the signaling pathways induced by GHRH to produce cancer, the structure activity relationship of GHRH-R antagonists and the resume of some in vitro and in vivo studies on the role of GHRH-R antagonists in the treatment of prostate cancer.

Berberine inhibits androgen synthesis by interaction with aldo-keto reductase 1C3 in 22Rv1 prostate cancer cells

AIdo-keto reductase family 1 member C3 has recently been regarded as a potential therapeutic target in castrate-resistant prostate cancer. Herein, we investigated whether berberine delayed the progression of castrate-resistant prostate cancer by reducing androgen synthesis through the inhibition of Aldo-keto reductase family 1 member C3. Cell viability and cellular testosterone content were measured in prostate cancer cells. Aido-keto reductase family 1 member C3 mRNA and protein level were detected by RT-PCR and Western bolt analyses, respectively. Computer analysis with AutoDock Tools explored the molecular interaction of berberine with Aldo-keto reductase family 1 member C3. We found that berberine inhibited 22Rvl cells proliferation and decreased cellular testosterone formation in a dose-dependent manner. Berberine inhibited Aldo-keto reductase family I member C3 enzyme activity, rather than influenced mRNA and protein expressions. Molecular docking study demonstrated that berberine could enter the active center of Aldo-keto reductase family 1 member C3 and form π-π interaction with the amino-acid residue Phe306 and Phe311. In conclusion, the structural interaction of berberine with Aldo-keto reductase family 1 member C3 is attributed to the suppression of Aldo-keto reductase family I member C3 enzyme activity and the inhibition of 22Rvl prostate cancer cell growth by decreasing the intfacellular androgen synthesis. Our result provides the experimental basis for the design, research, and development of AKRlC3 inhibitors using berberine as the lead compound.