Recent studies using mouse xenografts have shown that a testosterone albumin conjugate induced potent apoptotic regression of prostate tumors in vivo. In addition, testosterone BSA was selleck chemicals also reported to potentiate the paclitaxel mediated cytotoxicity both in vitro and in vivo. Based on these reports, on the expression patterns indicating predominant mAR mani festation in cancer cells and on the functional analysis of those receptors in colon cancer specimens and cell lines, we evaluated their potential biological role as drug targets in colon tumors in vivo. Interestingly, Inhibitors,Modulators,Libraries the chemically induced colon tumors were reduced by 65% in the testosterone HSA treated ani mals. Most probably this effect was due to the apoptotic regression of tumor cells as indicated by the TUNEL assay.

These results point out Inhibitors,Modulators,Libraries clearly that activation of mAR by testosterone HSA significantly affects the incidence of colon tumors in vivo. Interestingly, mAR is strongly expressed in tissues derived from p53 deficient xenograft tumors. Since p53 is a fre quently inactivated gene in tumors, it is interesting to hypothesize that mAR activation may result in eradication of p53 tumors in vivo. In addition, the detailed analysis of mAR expression in normal and cancer colon tissues iso lated from mice revealed clearly mAR over Inhibitors,Modulators,Libraries expression in tumor Inhibitors,Modulators,Libraries tissues, while in healthy specimens and non trans formed intestinal IEC06 cells mAR expression was unde tectable.

These findings support the notion that most probably normal cells will not respond to testo sterone HSA treatment, a conclusion supported by the TUNEL Inhibitors,Modulators,Libraries assay, that which indicated very low apoptotic response of normal tissues to testosterone HSA treatment, as well as from the failure of any pro apoptotic response in testosterone HSA treated IEC06 cells. Despite the fact that additional experi ments are required for the detailed evaluation of mAR dependent biological effects in colon cancer, our findings fully enforce the potential significance of the recently pos tulated notion that mAR may represent a novel and specific tumor target. In conclusion, the results presented here add a clear and significant piece of evidence to the potential anti tumori genic role of membrane androgen receptors. They indicate that a functional mAR are expressed not only in hor mone dependent tumors but also in colon tumors, b their activation through steroid albumin conjugates induces potent pro apoptotic responses regulated by cytoskeletal rearrangements, and c these receptors may represent specific targets for the development of novel drugs, since their activation drastically regresses tumor growth and tumor incidence in vivo.