6‐methylene progesterone is cytotoxic to human cancer cell lines independent of its 5‐α‐reductase activity

This investigation examined the effects of 6‐methylene progesterone (6MP), an irreversible inhibitor of 5‐α‐reductase, on prostatic cancer (PC) cell lines. Dose titration microculture tetrazolium assays were used to evaluate cytotoxicity in cultures treated for 72 hr with 6MP (0–20 μg/ml). An androgen‐sensitive cell line, LNCaP, was drug‐sensitive with a mean 50% lethal dose value (LD50) of 2.632 ± 0.103. Hormone‐resistant PC cell lines 1‐LN, DU 145, and PC3 also demonstrated sensitivity with LD50 values between 0.8579–1.110 μg/ml with a group average of 1.023 ± 0.082 μg/ml. Increasing dosages of dihydrotestosterone in the growth media did not alter 6MP cytotoxicity in androgen‐insensitive prostatic cancer cell lines. No correlation between androgen‐responsiveness and 6MP‐induced cytotoxicity was observed. In nonprostatic malignancies, 6MP inhibited adenocarcinoma cell lines with a mean group LD50 value of 0.7772 μg/ml ± 0.110. J82, a transitional cell carcinoma cell line of bladder origin, exhibited an average LD50 value of 1.041 ± 0.260. In an epidermoid cervical cancer cell line, ME180, an LD50 value of 0.5356 μg/ml ± 0.010 was noted. In a melanoma cell line, Du Mel 6, a mean LD50 of 0.7428 ± 0.023 μg/ml was achieved with 6MP. We conclude that 6MP, a novel 5‐α‐reductase inhibitor, has potential as a cytotoxic agent in prostatic carcinoma and additional human malignancies. Further study is justified.