A pyruvate decarboxylase-mediated therapeutic strategy for mimicking yeast metabolism in cancer cells

Bronwyn Scott, Jianliang Shen, Sara Nizzero, Kathryn Boom, Stefano Persano, Yu Mi, Xuewu Liu, Yuliang Zhao, Elvin Blanco, Haifa Shen, Mauro Ferrari, Joy Wolfram

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Cancer cells have high rates of glycolysis and lactic acid fermentation in order to fuel accelerated rates of cell division (Warburg effect). Here, we present a strategy for merging cancer and yeast metabolism to remove pyruvate, a key intermediate of cancer cell metabolism, and produce the toxic compound acetaldehyde. This approach was achieved by administering the yeast enzyme pyruvate decarboxylase to triple negative breast cancer cells. To overcome the challenges of protein delivery, a nanoparticle-based system consisting of cationic lipids and porous silicon were employed to obtain efficient intracellular uptake. The results demonstrate that the enzyme therapy decreases cancer cell viability through production of acetaldehyde and reduction of lactic acid fermentation.

Original languageEnglish (US)
Pages (from-to)413-421
Number of pages9
JournalPharmacological Research
Volume111
DOIs
StatePublished - Sep 1 2016

Keywords

  • Cancer metabolism
  • Multistage vector
  • Nanotechnology
  • Pyruvate decarboxylase
  • Warburg effect

ASJC Scopus subject areas

  • Pharmacology

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