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Cancer cells are exposed to a harsh microenvironment that is characterized by oxygen and nutrient deprivation. Hypoxic cancer cells are known to accumulate large quantities of lipids, particularly of triglycerides (TGs). Formation of lipid droplets –that contain triglycerides and cholesterol esters– is a hallmark of hypoxic cancer cells and is positively linked to the ability of cells to survive under oxidative stress. It has been shown that cancer cells have deregulated cholesterol metabolism. Some types of cancer cells have been shown to display increased cholesterol uptake, while others display increased de novo cholesterol synthesis. The effect of hypoxia on cholesterol accumulation has not been investigated in detail. A recent study has shown that hypoxia in combination with serum-deprivation induces overall decrease in cholesterol ester levels in colon and lung cancer cell. However, hypoxia (48hrs) alone was not able to induce any changes. It has been speculated that increasing the duration of hypoxia may have some impact on cholesterol accumulation in cancer cells. The presented work aimed to study the impact of varying durations of hypoxia on cholesterol content and cell proliferation rates in cancer cells. It was observed that cholesterol-load was slightly decreased after 48hours of hypoxia however this difference did not reach statistical significance. After 72 hour of hypoxia the cholesterol-load was same as under normoxic conditions. The cellular lipid-load was also assessed by Oil Red-O (ORO) staining which showed no visible differences between normoxic and hypoxic cells. To assess the underlying molecular mechanism the expression of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR) –the rate- limiting enzyme of mevalonate pathway– was also assessed. Again no significant difference was observed in HMGCR expression between normoxic and hypoxic cells. Further studies are required to understand the hypoxic regulation of cholesterol metabolism in cancer cells.
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