Succinic Acid Suppresses MLKL Transcripts in Endometrial Carcinoma Cells and Induces PGAM5 in Uterine Fibroblasts, with Antimicrobial Activity Against Selected Uterine Microorganisms

Background/Objectives: Succinic acid, a tricarboxylic acid cycle intermediate, is antiproliferative in endometrial cancer cells, where it previously increased RIPK1. We examined necroptosis pathway transcripts in endometrial carcinoma HEC-1B cells and non-malignant primary uterine fibroblasts (PUF), and antimicrobial activity against a limited uterine microbiota panel. Methods: Cells were exposed for 24 h to 640–5120 ng/mL succinic acid; lactate dehydrogenase (LDH) release was measured, and RIPK1, RIPK3, MLKL and PGAM5 transcripts quantified by RT-qPCR at 2560 ng/mL (21.7 µM). Results: In HEC-1B cells, LDH release rose fivefold at 5120 ng/mL but fell below vehicle at 2560 ng/mL; PUF was unchanged. At 2560 ng/mL, HEC-1B cells suppressed MLKL transcripts at least 30-fold without changing RIPK1, RIPK3 or PGAM5, whereas PUF cells induced PGAM5 24.8-fold and RIPK3 from a near-undetectable baseline. The vehicle induced RIPK1, RIPK3 and MLKL in HEC-1B cells, so comparisons were referenced to vehicle; directions were unchanged against untreated cells. Conclusions: Succinic acid inhibited all seven organisms in at least one solvent at 22–87 mmol/L, without demonstrable selectivity, about a thousand-fold above the transcriptionally active concentration. MLKL phosphorylation, protein abundance and viability were not measured, so these results describe transcriptional responses only and do not show that necroptotic execution changed.