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Batra 2022 Abstract Bioblast

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7.8. «5 min»
Batra Jyotsna
Subramaniam S, Jeet V, Gunter JH, Clements JA, Popat A, Batra Jyotsna (2022) Nano-encapsulated dichloroacetophenone (DAP), a regulator of essential mitochondrial enzyme, is a potential inhibitor of prostate cancer cell growth.
Bioblast 2022: BEC Inaugural Conference. In: https://doi.org/10.26124/bec:2022-0001 »Watch the presentation«

Link: Bioblast 2022: BEC Inaugural Conference

Subramaniam Sugarniya, Jeet Varinder, Gunter Jennifer H, Clements Judith A, Popat Amirali, Batra Jyotsna (2022)

Event: Bioblast 2022

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.

Keywords: Metabolism, Pyruvate dehydrogenase kinase 1, Dichloroacetophenone, Prostate cancer, Lactoferrin nanoparticle Bioblast editor: Plangger M


Affiliations

Sugarniya Subramaniam1,2,5, Varinder Jeet1,2,5, Jennifer H Gunter1,2,5Superscript text, Judith A Clements1,2,5, Amirali Popat3,4,5, Jyotsna Batra1,2,3
  1. School of Biomedical Sciences; Faculty of Health, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia
  2. Australian Prostate Cancer Research Centre-Queensland (APCRC-Q), Translational Research Institute, Queensland University of Technology, Woolloongabba, Australia
  3. School of Pharmacy, The University of Queensland, Brisbane, QLD, Australia
  4. Mater Research Institute, Woolloongabba, QLD, Australia
  5. Translational Research Institute, Woolloongabba, QLD, Australia - jyotsna.batra@qut.edu.au

Discussion

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Labels: MiParea: nDNA;cell genetics, Pharmacology;toxicology  Pathology: Cancer 




Coupling state: OXPHOS 


Event: B3