Development of glutathione depleting pro-oxidants for oxidative anticancer therapy
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초록
내용
Drug delivery systems play a important role to maximize the therapeutic efficacy of drugs. Cancer cells need to maintain a higher level of reactive oxygen species for metabolic and signaling aberrations and unrestrained growth. This altered redox balance makes a clear distinction between cancer cells and normal cells. In this work, we developed a B2C as a glutathione (GSH) depleting pro-oxidants by releasing quinone methide (QM) through esterase-mediated hydrolysis. So, B2C makes a higher oxidative stress than the threshold level which cancer cells can survive. High-degree of oxidative stress provoke mitochondrial disruption, activation of procaspase-3 and PARP-1, and cleavage of Bcl-2. In the animal study, intravenously injected B2C showed apoptotic cell death in tumors and greatly suppressed tumor growth. Given its cancer cell preferential toxicity and highly potent anticancer activity, B2C could be a potential candidate for oxidative anticancer therapy.