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

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Abstract

Purpose

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.

Procedures

We performed ORI of human melanoma DB-1 cells in culture and DB-1 mouse xenografts to detect the redox response to lonidamine (LND) treatment.

Results

For cultured cells, LND treatment for 45 min 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.

Conclusion

Our results support the utility of ORI for evaluating cellular metabolism and monitoring early metabolic response to cancer drugs.

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Acknowledgements

This work was supported by the NIH Grants R01CA155348 (L.Z. Li), R01CA191207 (L.Z. Li), R01-CA129544 (J. Glickson), and R01CA172820 (J. Glickson). We would also like to thank Ms. Lily Moon for technical assistance with mouse xenografts.

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Authors and Affiliations

  1. Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA

    He N. Xu, Min Feng, Kavindra Nath, David Nelson, Jeff Roman, Zhenwu Lin, Jerry Glickson & Lin Z. Li

  2. Britton Chance Laboratory of Redox Imaging, Johnson Research Foundation, Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, PA, USA

    He N. Xu, Min Feng, Zhenwu Lin & Lin Z. Li

  3. Institute of Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    He N. Xu & Lin Z. Li

  4. Department of Clinical Sciences, Temple University School of Medicine, Philadelphia, PA, USA

    Huaqing Zhao

  5. Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA

    Lin Z. Li

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  1. He N. Xu
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  2. Min Feng
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Correspondence to He N. Xu or Lin Z. Li.

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Xu, H.N., Feng, M., Nath, K. et al. Optical Redox Imaging of Lonidamine Treatment Response of Melanoma Cells and Xenografts. Mol Imaging Biol 21, 426–435 (2019). https://doi.org/10.1007/s11307-018-1258-z

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