Context-dependent effects of progesterone 4-pregnene metabolites on apoptosis and proliferation in ovarian cancer cell lines IGROV-1 and SK-OV-3.

Ovarian cancer remains the deadliest gynecological malignancy, with limited therapeutic options and high recurrence rates. Although progesterone (P4) metabolism has been implicated in hormone-related cancers, the biological roles of its 4-pregnene metabolites, 3α-dihydroprogesterone (3αHP) and 20α-dihydroprogesterone (20αHP), in ovarian cancer have not been explored. In this study, we investigated the effects of 3αHP and 20αHP on proliferation, apoptosis, migration, and clonogenic potential in two human ovarian cancer cell lines (IGROV-1 and SK-OV-3). Both metabolites significantly inhibited cell proliferation and clonogenicity. In IGROV-1 cells, 20αHP increased cleaved caspase-3 expression, and in SK-OV-3 increased early apoptosis, indicating pro-apoptotic activity. Neither compound altered cell migration in either cell line. These findings provide the initial evidence that 4-pregnene metabolites of progesterone modulate key features of ovarian cancer cell behavior, offering potential insights into alternative hormone-based therapeutic strategies.