Optical Redox Imaging of Lonidamine Treatment Response of Melanoma Cells and Xenografts.

Abstract

Fluorescence of co-enzyme reduced nicotinamide adenine dinucleotide (NADH) and oxidized flavoproteins (Fp) provides a sensitive measure of the mitochondrial redox state and cellular metabolism. By imaging NADH and Fp, we investigated the utility of optical redox imaging (ORI) to monitor cellular metabolism and detect early metabolic response to cancer drugs. We performed ORI of human melanoma DB-1 cells in culture and DB-1 mousexenografts to detect the redox response to lonidamine (LND) treatment. For cultured cells, LND treatment for 45min significantly lowered NADH levels with no significant change in Fp, resulting in a significant increase in the Fp redox ratio (Fp/(NADH+Fp)); 3-h prolonged treatment led to a decrease in NADH and an increase in Fp and a more oxidized redox state compared to control. Significant decrease in the mitochondrial redox capacity of LND-treated cells was observed for the first time. For xenografts, 45-min LND treatment resulted in a significant reduction of NADH content, no significant changes in Fp content, and a trend of increase in the Fp redox ratio. Intratumor redox heterogeneity was observed in both control and LND-treated groups. Our results support the utility of ORI for evaluating cellular metabolism and monitoring early metabolic response to cancer drugs.