Ferredoxin reductase affects p53-dependent, 5-fluorouracil–induced apoptosis in colorectal cancer cells

摘要: Loss of p53 gene function, which occurs in most colon cancer cells, has been shown to abolish the apoptotic response 5-fluorouracil (5-FU). To identify genes downstream that might mediate these effects, we assessed global patterns expression following 5-FU treatment isogenic cells differing only their status. The encoding mitochondrial ferredoxin reductase (protein, FR; gene, FDXR) was one few significantly induced by after treatment. FR protein localized mitochondria and suppressed growth when over-expressed. Targeted disruption FDXR human showed it essential for viability, partial resulted decreased sensitivity 5-FU-induced apoptosis. These data, coupled with effects pharmacologic inhibitors reactive oxygen species, indicate contributes p53-mediated apoptosis through generation oxidative stress mitochondria.