Alpha ketoglutarate (Akg), Potential Regulatorof Growth and Tumorigenesis in Breast cancer. Reviewingthe Recent Evidence.

Breast cancer is the most prevalent cancer in the world; Traditionaltreatments such as mastectomy, Radiation therapy andchemotherapy have been effective about ۹۰ % just in early stagesdiagnosis. The ways to prevent and treatment is noticeablefor researchers to find new ways and metabolites that have lessside effects than other aggressive treatments. Alpha ketoglutarate(Akg) as main intermediate of tricarboxylic acids (TCA) cycle,involves in wide range of physiological process especiallyimmunity against types of cancers.Recent studies about Akg effect on cancer cells have been shownpositive effects in reducing breast cancer cells growth and tumorigenesisby several ways. Akg dependent dioxygenases familyincludes two enzymes as Ten-eleven translocation (TET) andJumonji-C domain-containing family (JmjC) that are the largestfamily of histone demethylases. Accumulation of Akg due toα-ketoglutarate-dehydrogenase (αKGDH) inactivation triggersTET-۱ and TET-۳ protein expression and enzymatic activitythat leads to limiting cell migration and epithelial-mesenchymaltransition. In mouse models for breast cancer, Transketolase(TKT) and Akg enhanced the level of Tumor suppressor fumarate hydratase (FH) and succinate dehydrogenase and asresult, inhibited lung and lymph node metastasis. Akg is able toprevent metastasis of triple negative breast cancer by switchingtheir metabolism from glycolytic to oxidative metabolism byHypoxia Inducible Factors (HIF-۱) destabilization and by thisway prevents neoangiogenesis and induces apoptosis. Akg asan anti-proliferative of cancer cells metabolite, prevents DNAsynthesis, induces cell cycle arrest in G۱ phase and stimulateshistone demethylation by JmjC to induce senescence. Studieshighlight the importance of Akg and the need of more extensiveinvestigations to unveil the real potential of this metabolite as apossible therapeutic strategy for breast cancer treatment

کلیدواژه ها:

Alpha ketoglutarate ، Breast cancer ، Tumorigenesis ، Metastasis ، Hypoxia Inducible Factors