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- Batra 2022 Abstract Bioblast + (Our previous genetic studies identified Py … Our previous genetic studies identified Pyruvate Dehydrogenase Kinase 1 (PDK1) as a key gene regulated by microRNA in an allele dependent manner. Metabolic reprogramming is beneficial for tumour cell. We showed that PDK1 is an oncogene and plays a major role in glycolytic pathway in prostate cancer. Recently, targeting metabolic pathways with drugs has emerged as potential therapy in prostate cancer. In this study we found that DAP is more potent than dichloroacetate (DCA) in inhibiting prostate cancer cell proliferation, migration, colony formation and induced apoptosis. Further, DAP reduced extra cellular acidification rate in prostate cancer cells. In addition, lactoferrin conjugated DAP particle inhibited proliferation of prostate cancer cells at a low dose compared to DAP alone. DAP and lactoferrin conjugated DAP nanoparticles selectively caused a reduction in prostate cancer cell proliferation compared to normal derived cell line. Furthermore, lactoferrin conjugated DAP particles suppressed both glycolytic and oxidative phosphorylation pathway in prostate cancer cells. DAP and lactoferrin conjugated DAP particles suppressed the cell viability of docetaxel resistant cell line, PC3 RX-DT2R in a dose dependent manner. Overall, our results demonstrate that targeting glycolytic pathway via PDK1 by DAP could be therapeutic strategy in prostate cancer. Nanoparticle based DAP delivery may improve the efficiency in targeting prostate tumour metabolism.y in targeting prostate tumour metabolism.)
