Methionine gamma lyase from Clostridium sporogenes increases the anticancer effect of doxorubicin in A549 cells and human cancer xenografts

Invest New Drugs. 2019 Apr;37(2):201-209. doi: 10.1007/s10637-018-0619-4. Epub 2018 Jun 15.

Abstract

The anti-cancer efficacy of methionine γ-lyase (MGL) from Clostridium sporogenes (C. sporogenes) is described. MGL was active against cancer models in vitro and in vivo. The calculated EC50 values for MGL were 4.4 U/ml for A549, 7.5 U/ml for SK-BR3, 2.4 U/ml for SKOV3, and 0.4 U/ml for MCF7 cells. The combination of doxorubicin (DOX) and MGL was more effective for A549 human lung cancer growth inhibition than either agent alone in vitro and in vivo. MGL reduced the EC50 of doxorubicin from 35.9 μg/mL to 0.01-0.265 μg/mL. The growth inhibitory effect of DOX + MGL on A549 xenografts in vivo was reflective of the results obtained in vitro. The inhibition rate of tumor growth in the combined arm was 57%, significantly higher than that in the doxorubicin (p = 0.033)-alone arm.

Keywords: Cisplatin; Combined treatment; Doxorubicin; Methioninase; Methionine gamma lyase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Animals
  • Antibiotics, Antineoplastic / pharmacology
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Carbon-Sulfur Lyases / administration & dosage*
  • Cell Proliferation / drug effects
  • Cisplatin / pharmacology*
  • Clostridium / enzymology*
  • Doxorubicin / pharmacology*
  • Drug Synergism*
  • Female
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasms / drug therapy*
  • Neoplasms / enzymology
  • Neoplasms / pathology
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • Antibiotics, Antineoplastic
  • Antineoplastic Agents
  • Doxorubicin
  • Carbon-Sulfur Lyases
  • L-methionine gamma-lyase
  • Cisplatin

Supplementary concepts

  • Clostridium sporogenes