Modulation of Ovarian Cancer Cell Metabolism via Pyruvate Kinase M2 (PKM2) and Glucose Deprivation

Abstract

Ovarian cancer is one of the most aggressive types of cancer in women. While the molecular mechanisms of ovarian cancer have been extensively studied, treatments for ovarian cancer are still limited. Understanding the metabolism of ovarian cancer cells has been of great interest to many scientists. Cancer cells express a higher consumption rate of glucose which results in accumulation of lactate even in an oxygenized environment. This alteration in metabolism is known as the Warburg effect and is necessary for the growth and survival of cancer cells. Pyruvate kinase M2 or PKM2 has been shown to be a regulator enzyme responsible for the conversion of PEP to pyruvate. Recent studies have demonstrated that PKM2 is over‐expressed in tumor cells. However, its functions are yet to be elucidated. In this project, we investigated the effects of glucose deprivation on ovarian cancer cells (CaOV3 cell line). The results showed that reduction of glucose supply in culture medium affects cells morphologically and metabolically. MTT assay data showed that glucose alters cellular proliferation in a dose dependent manner. Lower glucose supply results in alkalinization of culture medium. Seahorse data indicated that glucose deprivation reduces oxygen consumption rate of ovarian cancer cells. Western blot analysis and confocal microscopy demonstrated that PKM2 expression is altered in the cytoplasm in response to glucose deprivation. PKM2 levels decrease 30 mins post 1 mM glucose treatment, reaches to the lowest at 1 hr, recovering within 2 hrs. Collectively, our data suggest that PKM2 may be a molecular target for ovarian cancer treatment and glucose deprivation may be a potential approach for modulation of PKM2.