Emodin Down-Regulates Androgen Receptor and Inhibits Prostate Cancer Cell Growth

Abstract

Hormone-refractory relapse is an inevitable and lethal event for advanced prostate cancer patients after hormone deprivation. A growing body of evidence indicates that hormone deprivation may promote this aggressive prostate cancer phenotype. Notably, androgen receptor (AR) not only mediates the effect of androgen on the tumor initiation but also plays the major role in the relapse transition. This provides a strong rationale for searching new effective agents targeting the down-regulation of AR to treat or prevent advanced prostate cancer progression. Here, we show that emodin, a natural compound, can directly target AR to suppress prostate cancer cell growth in vitro and prolong the survival of C3(1)/SV40 transgenic mice in vivo. Emodin treatment resulted in repressing androgen-dependent transactivation of AR by inhibiting AR nuclear translocation. Emodin decreased the association of AR and heat shock protein 90 and increased the association of AR and MDM2, which in turn induced AR degradation through proteasomemediated pathway in a ligand-independent manner. Our work indicates a new mechanism for the emodin-mediated anticancer effect and justifies further investigation of emodin as a therapeutic and preventive agent for prostate cancer. (Cancer Res 2005; 65(6): 2287-95)

Screening for novel quorum-sensing inhibitors to interfere with the formation of Pseudomonas aeruginosa biofilm

“…The result was consistent with that of halogenated furanones on LuxR protein turnover (Manefield et al, 2002) and that of P. aeruginosa on TraR degradation (Zeng et al, 2008). It has also been reported that emodin can inhibit androgen receptor (AR) transcriptional activity, resulting in AR degradation through a proteasome-mediated pathway and suppressing prostate cancer cell growth in vitro (Cha et al, 2005).…”

“…It also promotes the apoptosis of human breast cancer BCap-37 cells . Some studies have also reported the effect of emodin on cell death in human prostate, lung, liver, cervical and blood cancer cells (Cha et al, 2005;Su et al, 2005;Jing et al, 2006;Fu et al, 2007;Muto et al, 2007). In this study, compound 5 (emodin) and ampicillin acted jointly against P. aeruginosa more effectively than either of them did alone, suggesting that compound 5 enhanced the activity of ampicillin against P. aeruginosa.…”

Emodin As an Effective Agent in Targeting Cancer Stem-Like Side Population Cells of Gallbladder Carcinoma

“…Emodin has long been studied for anti-inflammatory, antibacterial, diuretic, immunosuppressive, and chemopreventive effects. The anticancer effect of emodin is found to be mediated via induction of apoptosis, inhibition of cancer cell growth, antiproliferation, and antiadhesion [22,39,40]. Recently, we have found that emodin can facilitate cytotoxicity in gallbladder carcinoma in the ROS-dependent manner [21].…”

“…SP and non-SP cells were harvested, washed, and resuspended in serumfree optimum medium and then injected subcutaneously into 6-week-old BALB/c-nu/nu mice (n = 6 mice per group, purchased from Shanghai Experimental Animal Center). Tumor size was measured every 2 days with a caliper, and tumor volumes were calculated using the formula [22]: p/ 6 · a · b 2 , where a and b were the long and short diameters, respectively. When tumor size of respective cell transplantation model was *100 mm 3 , mice were sorted into 4 equal groups.…”

Androgen receptor and prostate cancer

“…42 Therapeutic approaches facilitating AR degradation by the ubiquitin-proteasome pathway may open new avenues in CaP medicine. 43 Although, not fully understood, blockade of the proteasome pathway by hyperthermia or specific blockers may also have future therapeutic values. 44 Reducing AR protein levels in CaP may become a powerful strategy in CaP treatment.…”