Starving Cancer: a Study of Glutamine Dependency in Cancer Cells

This study examined glutamine dependency in cancer cells, where glutamine serves as the primary mitochondrial energy source. Effects of the protein cyclin D1 on glutamine metabolism were examined because cyclin D1 is a major driver of cancer-cell proliferation. Specific goals were 1) to find human cancer-cell lines that are glutamine dependent, 2) to knock down glutamine and overexpress cyclin D1 in each glutamine-dependent cell line, and 3) to determine effects of overexpression of cyclin D1 on viability of glutamine-dependent cells in absence of glutamine. Three cancer-cell lines were tested for glutamine dependency: SkHep liver-cancer cells, LnCap prostate-cancer cells, and HUH7 liver-cancer cells. Cell culturing, viability tests, protein assays, and Western blots were used to identify which of these cell lines are glutamine dependent and to determine effects of cyclin D1 overexpression on this dependency. Viability tests showed that both healthy AML12 mouse cells (control) and SkHep cancer cells are glutamine dependent, whereas LnCap and HUH7 are not. Results suggest that viability of glutamine-starved SkHep cancer cells significantly decreases (p = 0.0019) when cyclin D1 is overexpressed and significantly increases when cyclin D1 is knocked down (p = 0.05). On the other hand, AML12 cell viability significantly increases when cyclin D1 is overexpressed (p = 0.0018) and significantly decreases (p = 0.0407) when cyclin D1 is knocked down. These results show an interesting difference between glutamine-dependent cancer cells and healthy cells that may be exploited to target glutamine-dependent cancer cells.