title: A pyruvate decarboxylase-mediated therapeutic strategy for mimicking yeast metabolism in cancer cells.
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.
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030, USA.
authors.forename: Bronwyn
authors.initials: B
authors.lastname: Scott
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030, USA.
authors.forename: Jianliang
authors.initials: J
authors.lastname: Shen
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030, USA; Applied Physics Graduate Program, Rice University, Houston, TX 77005, USA.
authors.forename: Sara
authors.initials: S
authors.lastname: Nizzero
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030, USA.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Boom
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030, USA.
authors.forename: Stefano
authors.initials: S
authors.lastname: Persano
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Mi
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030, USA.
authors.forename: Xuewu
authors.initials: X
authors.lastname: Liu
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, National Center for Nanoscience & Technology of China, University of Chinese Academy of Sciences, Beijing 100190, China; Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Yuliang
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030, USA.
authors.forename: Elvin
authors.initials: E
authors.lastname: Blanco
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030, USA; Department of Cell and Developmental Biology, Weill Cornell Medicine, New York, NY 10065, USA.
authors.forename: Haifa
authors.initials: H
authors.lastname: Shen
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030, USA; Department of Medicine, Weill Cornell Medicine, New York, NY 10065, USA. Electronic address: mferrari@houstonmethodist.org.
authors.forename: Mauro
authors.initials: M
authors.lastname: Ferrari
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030, USA; CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, National Center for Nanoscience & Technology of China, University of Chinese Academy of Sciences, Beijing 100190, China. Electronic address: jvwolfram@houstonmethodist.org.
authors.forename: Joy
authors.initials: J
authors.lastname: Wolfram
mesh_terms: D000079:Acetaldehyde / Q000378:metabolism; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers; D004339:Drug Compounding; D004734:Energy Metabolism / Q000187:drug effects*; D005260:Female; D005285:Fermentation; D006019:Glycolysis; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism; D008055:Lipids / Q000737:chemistry; D053758:Nanoparticles; D016062:Porosity; D011767:Pyruvate Decarboxylase / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D012825:Silicon / Q000737:chemistry; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008055:Lipids; D029701:Saccharomyces cerevisiae Proteins; D019344:Lactic Acid; D011767:Pyruvate Decarboxylase; D000079:Acetaldehyde; D012825:Silicon
keywords: Cancer metabolism; Multistage vector; Nanotechnology; Pyruvate decarboxylase; Warburg effect