Growth modulatory effects of some 6-methylenic steroids on human and hamster pancreatic adenocarcinoma cells in vitro.
Similarities between pancreatic, prostate and mammary tumors in possession of steroidal receptors and enzymes led to investigation of the responsiveness of pancreatic cancer to steroids with potential for tumor inhibition. The compounds were tested in vitro against human (HPAF and PANC-1) and hamster (HP-1) pancreatic ductal tumor cell lines using a colorimetric enzyme-based assay (MTT) to assess both cytotoxic and cytostatic effects and the 3H-thymidine uptake assay for cytostatic effects. Only certain 6-methylenic steroidal 3-ketones and the anti-estrogen tamoxifen citrate exerted appreciable anti-tumor effects. Marked cytotoxic and cytostatic activity was shown by some 6-methylenic congeners of progesterone, testosterone and its acetate, and 4-androstene-3,17-dione on both human and hamster pancreatic tumor cell lines. In contrast to prostate cancer, testosterone, but not 5 alpha-dihydrotestosterone, enhanced growth of the well differentiated HPAF cell line as well as the poorly differentiated PANC-1 cell line. It is therefore surprising that the 6-methylene derivative of testosterone acetate, which is both a potent androgen and 5 alpha-reductase inhibitor, is a very active tumor inhibitor in our assay.
Selvan
R S
RS
Department of Microbiology, Duke University Medical Center, Durham, NC 27710.
Metzgar
R S
RS
Petrow
V
V
D000818:Animals; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000188:drug therapy* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D006224:Cricetinae; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013256:Steroids / Q000737:chemistry / Q000494:pharmacology*; D013778:Tetrazolium Salts; D013844:Thiazoles; D013936:Thymidine; D014407:Tumor Cells, Cultured
D013256:Steroids; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue; D013936:Thymidine