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Ovarian cancer remains one of the most aggressive types of cancer in women. While the molecular mechanisms of the invasiveness of ovarian cancer have been extensively studied, the 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 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 level starts to decrease 30min post 1 mM glucose treatment, reaches to the lowest at 1 hour, and recovers within 2 hours. Collectively, our data suggest that PMK2 may be a molecular target for ovarian cancer treatment and glucose deprivation may be a potential approach for modulation of PKM2.  
Novel discovery
JustinianoJeanine2016WanYinshengBiology
  
UV radiation and oxidative stress have been shown to be related to skin aging and skin cancer. Our previous studies have demonstrated that UV radiation induces generation of reactive oxygen species that leads to MAP kinase activation and MMP expression with a result of collagen reduction in cultured human skin keratinocytes in vitro and in human skin in vivo. We have also found that UV radiation and oxidative stress induces dehydration in human skin cells. Existing data have indicated that oxidative stress may alter cellular metabolism. We hypothesized that UV radiation and oxidative stress may also change metabolism in skin cells. Here we examined the effects of UV radiation and hydrogen peroxide on the metabolism of cultured human skin keratinocytes (HaCat cells). Western blot analysis showed that UV radiation inactivates PKM2 in keratinocytes in a time dependent manner. Seahorse data showed that UV radiation and H2O2 treatments decrease oxygen consumption rate (OCR) in HaCat cells. mTOR inhibitor Rapamycin increases oxygen consumption in both untreated and H2O2 treated cells. However, ERK inhibitor U0126 increases OCR in untreated cells, but decreases in H2O2-treated cells. PKM2 activator DASA increases OCR in untreated cells but decreases OCR in H2O2 treated cells.  Given that H2O2 is a recognized inhibitor of PKM2, we conclude that inhibition of PKM2 by UV radiation and oxidative stress may directly affect oxygen consumption and glycolysis in human skin cells.
novel discovery
GarrityRyan2016WanYinshengBiology