Colorectal cancer hallmark, low molecular weight protein tyrosine phosphatase, is downmodulated by mitoxantrone

Along tumor development, cells acquired biological plasticity, defined as hallmarks of cancer, which contribute for the disease complexity and aggressiveness. Our group and others have shown the relevance of the low molecular weight protein tyrosine phosphatase (LMWPTP) in mediating cancer plasticity, resistance and metastasis. Under molecular aspect, this phosphatase favors Warburg effect. In this study, we aimed to investigate the responsiveness of colorectal cancer spheroids towards mitoxantrone (MTX) through assessing viability (MTT assay) and amount of key proteins involved in glucose metabolism reprogramming (Western blot). Spheroids that display higher level of LMWPTP were better responders to MTX (15 µM) than the ones having lower basal level of this enzyme. Interestingly, the MTX treatment dropped the amount of LMWPTP. Accordingly, lactate dehydrogenase was inhibited, and mitochondrial proteins were augmented. Our findings showed that despite intercalating DNA and inhibiting topoisomerase, MTX decreases the amount of LMWPTP, and consequently, disrupting Warburg effect.