title: Bongkrekic Acid as a Warburg Effect Modulator in Long-term Estradiol-deprived MCF-7 Breast Cancer Cells.
abstract: An in vitro cell model of long-term estrogen-deprived MCF-7 (LTED) cells has been utilized to analyze the re-growth mechanisms of breast cancers treated with blockers for estrogen receptor α (ERα) signaling. Bongkrekic acid (BKA) is a natural toxin isolated from coconut tempeh contaminated with the bacterium Burkholderia cocovenans.
  
  
  
  LTED cells, MCF-7 cells and MDA-MB-231 cells were employed in the study. After treatment with BKA (chemically synthesized; purity: >98%), several biochemical analyses were carried out.
  
  
  
  LTED cells were categorized into an oxidative phenotype. When LTED cells were treated with BKA, lactate dehydrogenase A (LDH-A)/pyruvate dehydrogenase kinase 4 (PDK4) were down-regulated, thereby prompting the aggressive use of glucose via mitochondrial oxidative phosphorylation and induction of cell death responses. These effects of BKA were not observed in the other breast cancer cells analyzed.
  
  
  
  We suggest the potential of BKA as an experimental tool for the analysis of cancer biology in LTED cells.
authors: Laboratory of Xenobiotic Metabolism and Environmental Toxicology, Faculty of Pharmaceutical Sciences, Hiroshima International University (HIU), Hiroshima, Japan.|Department of Molecular Biology, Daiichi University of Pharmacy, Fukuoka, Japan.
authors: Shuso
authors: S
authors: Takeda
authors: Department of Molecular Biology, Daiichi University of Pharmacy, Fukuoka, Japan.
authors: Hiroyuki
authors: H
authors: Okazaki
authors: Department of Molecular Biology, Daiichi University of Pharmacy, Fukuoka, Japan.
authors: Taichi
authors: T
authors: Kudo
authors: Department of Molecular Biology, Daiichi University of Pharmacy, Fukuoka, Japan.
authors: Kazuhiro
authors: K
authors: Kakizoe
authors: Department of Molecular Biology, Daiichi University of Pharmacy, Fukuoka, Japan.
authors: Taichi
authors: T
authors: Himeno
authors: Institute for Materials Chemistry and Engineering, Kyushu University, Kasuga, Japan.
authors: Kenji
authors: K
authors: Matsumoto
authors: Institute for Materials Chemistry and Engineering, Kyushu University, Kasuga, Japan.
authors: Mitsuru
authors: M
authors: Shindo
authors: Department of Molecular Biology, Daiichi University of Pharmacy, Fukuoka, Japan haramaki@daiichi-cps.ac.jp.|Drug Innovation Research Center, Daiichi University of Pharmacy, Fukuoka, Japan.
authors: Hironori
authors: H
authors: Aramaki
mesh_terms: D000951:Antigens, Neoplasm / Q000235:genetics; D001865:Bongkrekic Acid / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism*; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics; D045744:Cell Line, Tumor; D004250:DNA Topoisomerases, Type II / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D015536:Down-Regulation; D004958:Estradiol; D005260:Female; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D019394:Ki-67 Antigen / Q000235:genetics; D007770:L-Lactate Dehydrogenase / Q000235:genetics; D000080864:Lactate Dehydrogenase 5; D008928:Mitochondria / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase
chemical_list: D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D007527:Isoenzymes; D019394:Ki-67 Antigen; C000631432:PDK4 protein, human; D047495:PPAR gamma; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D001865:Bongkrekic Acid; D004958:Estradiol; D007770:L-Lactate Dehydrogenase; D000080864:Lactate Dehydrogenase 5; C577474:CPT1A protein, human; D002334:Carnitine O-Palmitoyltransferase; D017346:Protein Serine-Threonine Kinases; D004250:DNA Topoisomerases, Type II; D005947:Glucose
keywords: BKA; Bongkrekic acid; LDH-A; LTED cells; MTS assay; NADH; PDK4