CHED 844 |
| Flexible heteroarotinoids (flex-hets), a novel class of retinoid anti-cancer drug, induce apoptosis in multiple types of cancer cells. The lead flex-het, SHetA2, is a powerful inhibitor of oxygen consumption in actively respiring mitochondria isolated from A2780 ovarian cancer cells. The effect of the drug on mitochondrial function was assessed using sub-mitochondrial particles (SMP's) isolated from bovine heart muscle. NADH oxidase activity in the absence of ubiquinone was assayed spectrophotometrically, using the decrease in absorbance of NADH at 340nm. Treatment with varying concentrations of SHeta2 inhibited NADH oxidase activity in a dose dependent fashion. Full Complex I activity, assessed in the presence of added ubiquinone analog UQ1, was also inhibited by addition of drug. Preliminary steady state kinetic analysis suggests that flex-hets are mixed inhibitors of Complex I. The apparent maximum velocity (Vmax') is decreased and the Michaelis-Menten constant (km') is increased on treatment with flex-het drug. |
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Undergraduate Research Poster Session: Biochemistry
2:00 PM-4:00 PM, Monday, April 7, 2008 Morial Convention Center -- Hall A, Poster
Division of Chemical Education |