Berberine Suppresses Androgen Receptor Signaling in Prostate Cancer

Abstract

The androgen receptor (AR) is critical in the normal development and function of the prostate, as well as in prostate carcinogenesis. Androgen deprivation therapy is the mainstay in the treatment of advanced prostate cancer, however, after an initial response, the disease inevitably progresses to castration-resistant prostate cancer (CRPC). Recent evidence suggests that continued AR activation, sometimes in a ligand-independent manner, is commonly associated with the development of CRPC. Thus, novel agents targeting the AR are urgently needed as a strategic step in developing new therapies for this disease state. In this study, we investigated the effect of berberine on AR signaling in prostate cancer. We report that berberine decreased the transcriptional activity of AR. Berberine did not affect AR mRNA expression, but induced AR protein degradation. Several ligand-binding domain truncated AR splice variants have been identified and these variants are believed to promote the development of CRPC in patients. Interestingly, we found that these variants were more susceptible to berberine-induced degradation than the full-length AR. Furthermore, the growth of LNCaP xenografts in nude mice was inhibited by berberine and AR expression was reduced in the tumors, whereas the morphology and AR expression in normal prostates were not affected. This report is the first to show that berberine suppresses AR signaling and suggests that berberine or its derivatives is a promising agent for the prevention and/or treatment of prostate cancer.

Berberine inhibits the LPS‑induced proliferation and inflammatory response of stromal cells of adenomyosis tissues mediated by the LPS/TLR4 signaling pathway

“…BBR as an isoquinoline derivative alkaloid has been demonstrated to have diverse pharmacological activities involving multiple biological mechanisms, which may be utilized for the treatment of a wide variety of diseases (9)(10)(11)(12)(13)(14). Previous studies have demonstrated that BBR acts as an LPS antagonist and blocks LPS/TLR4 signaling in an LPS-induced animal model (28)(29)(30).…”

“…Studies have demonstrated that BBR possesses different pharmacological activities involving multiple biological mechanisms, and may be utilized for the treatment of various diseases, including diabetes, metabolic syndrome and various types of cancer (9)(10)(11)(12)(13)(14). It was reported that BBR has a beneficial effect on patients with diabetes and obesity, partly by stimulating adenosine monophosphate kinase activity (15).…”

Berberine Induces Senescence of Human Glioblastoma Cells by Downregulating the EGFR–MEK–ERK Signaling Pathway

“…Berberine can induce apoptosis in a variety of cancer cells (12,13,(18)(19)(20). We, therefore, determined whether berberine could also induce apoptosis of glioblastoma cells.…”

“…It is shown to possess anticancer activities against various types of cancer cells. Berberine can induce apoptosis and cell-cycle arrest of tumor cells (10)(11)(12)(13)(14). In this report, we studied the effect of berberine on glioblastoma cells in vitro and on tumor xenografts.…”

Berberine-induced anticancer activities in FaDu head and neck squamous cell carcinoma cells

“…Recent pharmacological studies of berberine have demonstrated that this molecule alleviates diabetic nephropathy (13), rheumatoid arthritis (14), and inflammation (15). Moreover, berberine has antioxidant effects (16,17), prevents obesity (18), and has anticancer activities in breast (19), prostate (20), cervical (21), gastric (22), oral (23,24), and ovarian cancers (25). Although these anticancer effects of berberine and associated cell signaling pathways have been reported in various cancers, the effects of berberine on apoptosis have not been reported in HNSCC.…”