Methylglyoxal at metronomic doses sensitizes breast cancer cells to doxorubicin and cisplatin causing synergistic induction of programmed cell death and inhibition of stemness

Biochemical Pharmacology
Anirban RoyManju Ray

Abstract

Potent anticancer activity coupled with absence of toxicity at therapeutic dose established the glycolytic metabolite, methylglyoxal, as a promising candidate against malignant neoplasia. In this preclinical study we illustrate the applicability of methylglyoxal in formulating an optimally designed combination regimen with chemotherapeutic drugs against breast cancer. Results demonstrated a synergistic augmentation in doxorubicin and cisplatin mediated cytotoxicity in human breast cancer cell lines MDA MB 231 & MCF 7 with methylglyoxal co-treatment at metronomic concentrations. The cell death due to combination treatment was significantly prevented by N-Acetylcysteine and the synergistic effects were attenuated in presence of inhibitors for apoptosis and necroptosis, in MDA MB 231 and MCF 7 cells, respectively. Additionally, acridine orange staining and immunoblotting with LC3B antibody indicated the suppression of doxorubicin induced autophagy flux with methylglyoxal co-treatment. This report documents for the first time the preferential targeting of breast cancer stem cells by methylglyoxal. Combination treatment with doxorubicin or cisplatin hindered mammosphere forming efficiency and inclusively eliminated both cancer stem ...Continue Reading

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Nov 23, 2018·Naunyn-Schmiedeberg's Archives of Pharmacology·Amira SalehWaleed Barakat
Jun 5, 2020·Journal of Receptor and Signal Transduction Research·Zengjun XieLiang Zhao
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Apr 20, 2021·Frontiers in Oncology·Alessia LeoneClaudia Miele
Oct 31, 2021·Molecular and Cellular Biochemistry·Minakshi BediAlok Ghosh

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