Therapeutic targeting of the tryptophan-kynurenine-aryl hydrocarbon receptor pathway with apigenin in MED12-mutant leiomyoma cells.

Approximately 77.4% of uterine leiomyomas carry MED12 gene mutations (mut-MED12), which are specifically associated with strikingly upregulated expression and activity of the tryptophan 2,3-dioxygenase (TDO2) enzyme, leading to increased conversion of tryptophan to kynureine. Kynurenine increases leiomyoma cell survival by activating the aryl hydrocarbon receptor (AHR).

Stearoyl-coenzyme A desaturase enhances cell survival in human uterine leiomyoma.

Objective: Stearoyl-CoA desaturase (SCD1) is an enzyme that catalyzes the conversion of saturated delta-9 fatty acids to monounsaturated fatty acids. SCD1 is highly expressed in various cancers and facilitates cancer cell survival, tumor growth, and metastasis. This study aimed to assess SCD1 expression and function in uterine leiomyoma and matched myometrial tissue and evaluate the impact of SCD1 inhibition on leiomyoma cell viability and apoptosis.