Influence of high glucose state on bromopyruvate-induced cytotoxity by human colon cancer cell lines

Drug Metab Pharmacokinet. 2016 Feb;31(1):67-72. doi: 10.1016/j.dmpk.2015.10.006. Epub 2015 Nov 26.

Abstract

Background: Attention must be paid to chemotherapy for cancer patients in a hyperglycemia state. It is difficult for chemotherapy to cure cancer in patients in a hyperglycemia state. This study was carried out to determine the change in cell viability after treatment with bromopyruvate, which is an alkylating drug with anti-tumor activity, in a high glucose condition.

Methods: The function of l-lactate and bromopyruvate transport was studied using human colon cancer cell lines (LoVo and HT-29) and radiolabeled l-lactate and bromopyruvate. Cell viability was monitored by the trypan blue exclusion assay. The expression level of human monocarboxylate transporter 1 (hMCT1) was evaluated by Western blot analysis.

Results: Bromopyruvate-induced cell death was suppressed by a high glucose condition. l-Lactate and bromopyruvate uptake were suppressed by a high glucose condition. hMCT1 as a bromopyruvate carrier was functionally expressed in the cells. However, the expression of hMCT1 was suppressed by a high glucose state.

Conclusions: Down-regulation of hMCT1 by a high glucose state is one of the possibilities of the bromopyruvate resistance. We should pay scrupulous attention to cancer chemotherapy for patients who have developed diabetes.

Keywords: Bromopyruvate; Glucose; Lactate transporter; Tumor cells.

MeSH terms

  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / pharmacology
  • Cell Death / drug effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Colonic Neoplasms / drug therapy
  • Colonic Neoplasms / metabolism*
  • Down-Regulation / drug effects
  • Glucose / metabolism*
  • Humans
  • Lactic Acid / metabolism
  • Pyruvates / adverse effects*
  • Pyruvates / pharmacology

Substances

  • Antineoplastic Agents
  • Pyruvates
  • Lactic Acid
  • bromopyruvate
  • Glucose