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Does 2DG-SUC-ADM reduce organ toxicity and enhance antitumor efficacy compared with free Adriamycin in preclinical models?
Does 2DG-SUC-ADM reduce organ toxicity and enhance antitumor efficacy compared with free Adriamycin in preclinical models?
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A novel 2-deoxyglucose-based adriamycin complex demonstrates enhanced antitumor efficacy and reduced organ toxicity in preclinical models, offering a potential strategy to mitigate adriamycin-induced cardiotoxicity.
Adriamycin (ADM) has been effective against many types of solid tumors in clinical applications. However, its use is limited because of systemic toxicities, primarily cardiotoxicity, and multidrug resistance. In this study, a new active receptor-mediated complex, ADM conjugated with 2-amino-2-deoxy-d-glucose and succinic acid (2DG-SUC-ADM), was designed to target tumor cells through glucose transporter 1 (GLUT1). MTT assay and confocal images showed that the complex had better inhibition rate to tumor cells and low toxicity to normal cells. Most importantly, the complex displayed a potential to reverse overcome multidrug resistance in cancer cells, with more complex transported into the nucleus of tumor cells. Our in vivo experiments also showed that this new complex could significantly decrease organ toxicity and enhance the antitumor efficacy compared with free ADM, indicating a promising drug of 2DG-SUC-ADM for targeted cancer therapy.
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Cao et al. (2013) studied this question.
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