Approaches to prostatic cancer chemotherapy using the Dunning R3327H prostatic adenocarcinoma.
Androgen-responsive cells: To determine if testosterone or dihydrotestosterone is the main trophic hormone of prostatic adenocarcinoma, we have treated Dunning R3327H prostatic adenocarcinoma-bearing rats with 6-methylene progesterone, which blocks conversion of testosterone to dihydrotestosterone. Copenhagen-Fisher rats were treated with steroid (20 mg/Kg daily) immediately following implantation of tumor and thereafter for 117 days. There was a 92% inhibition of growth of tumors and a lesser effect upon prostate and seminal vesicles. Tumor-free body weights remained unchanged. Both treated and untreated tumors had equivalent DNA content on a per weight basis. This result supports the thesis that prostatic adenocarcinoma requires dihydrotestosterone for growth. Androgen-insensitive cells: Advanced prostate cancer does not respond to endocrine therapy but is temporarily controlled by the cytotoxic steroid estramustine. The latter shows significant selective binding to prostatic protein. To develop chemotherapeutic agents that will control androgen-insensitive cells and possess improved selectivity for prostatic protein, we have studied a number of steroids for their ability to displace 3H-labeled estramustine from prostatic cytosolic proteins. Surprisingly, a carbamido substituent at the C17 position was found to confer significant binding affinity for prostatic estramustine-binding protein. Extension of this structural characteristic to the estramustine type of molecule is being studied.
D058891:5-alpha Reductase Inhibitors; D000230:Adenocarcinoma / Q000188:drug therapy*; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D004961:Estramustine / Q000378:metabolism; D008297:Male; D009368:Neoplasm Transplantation; D009929:Organ Size / Q000187:drug effects; D011374:Progesterone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011467:Prostate / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D029584:Prostatic Secretory Proteins; D051381:Rats; D013329:Structure-Activity Relationship
D058891:5-alpha Reductase Inhibitors; D002352:Carrier Proteins; D029584:Prostatic Secretory Proteins; C028321:estramustine-binding protein; C036790:6-methylene-4-pregnene-3,20-dione; D004961:Estramustine; D011374:Progesterone