Succinic acid might be an inducement for the road to RIPK for death through necroptosis in endometrium cancer

Background: Succinic acid, a natural agent has gained attention in cancer research. It induces apoptotic cell death in endometrial cancer. Our aim was to understand the specific cellular pathway triggered by succinic acid at the molecular level. Methods: The seventeen genes involved in death pathways were examined by real time quantitative reverse transcription polymerase chain reaction (RT-qPCR) after treating endometrial cancer (CRL-2923) and healthy (MRC-5) cells with 5 µM and 10 µM of succinic acid. Apoptotic relationship was analyzed with the cell death detection Enzyme-Linked Immunosorbent Assay (ELISA) kit to understand the effects of succinic acid on survival. Results: The gene expression of tumor necrosis factor receptor superfamily member 10b (TNFRSF10B) and mitochondrial carrier 1 (MTCH1) increased by 3.62 and 3.31-folds, respectively, after adding 5 µM of succinic acid to CRL-2923 cells. A 9.94-fold upregulation was measured by the changes in the receptor-interacting serine/threonine kinase 1 (RIPK) gene (p = 0.008). The necrotic members, poly (ADP-ribose) polymerase 1 (PARP1) and mixed lineage kinase domain like pseudokinase (MLKL), genes expression decreased after adding 5 and 10 µM of succinic acid, particularly 10 µM succinic acid exhibited a 4.11-fold decrease in the expression of the PARP1 gene. Conclusions: The intersections of the death pathways form a valuable key spot for cancer treatment. After succinic acid treatment, the interaction between the death pathways with RIPK gene have shown promising results for RIPK family. Ultimately, elucidating these cellular pathways, whose functionality is important in every physiological or pathological situation, by evaluating them from different perspectives is among the important needs of the current literature. Therefore, the effects of succinic acid via RIPK should be considered for targeting and/or modulating.

Succinic acid; Endometrial cancer; Cell death; Necroptosis; RIPK

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