Mechanism of sensitivity of cultured pancreatic carcinoma to asparaginase

Int J Cancer. 1978 Dec;22(6):728-33. doi: 10.1002/ijc.2910220615.

Abstract

The effects of E. coli L-asparaginase on cultured human pancreatic carcinoma (MIA PaCa-2) have been studied. The enzyme (1 U/ml) inhibited growth and protein synthesis in both MIA PaCa-2 and PANC-1, another pancreatic carcinoma cell line, but had little or no effect on human breast carcinoma or melanoma cells. The inhibition of protein synthesis by E. coli L-asparaginase was largely reversed by L-glutamine but not by L-asparagine. The growth of both MIA PaCa-2 and PANC-1 showed absolute dependence on L-glutamine. These results indicate that the effect of E. coli L-asparaginase on cultured pancreatic carcinoma cells is exerted at least in part through its L-glutaminase activity. Although the addition of L-glutamine to the culture appeared to prevent cell death caused by L-asparaginase, it did not restore the ability of the cells to proliferate. Asparaginase derived from vibrio succinogenes, which is virtually free of L-glutaminase activity, was equally inhibitory to MIA PaCa-2 cell growth but did not affect protein synthesis. It is concluded that the inhibition of growth of cultured pancreatic carcinoma cells by E. coli asparaginase is a combined function of both its L-asparaginase and L-glutaminase activity.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acids / metabolism
  • Asparaginase / pharmacology*
  • Asparagine / pharmacology
  • Breast Neoplasms / metabolism
  • Cell Line
  • Cell Survival / drug effects*
  • Cells, Cultured
  • DNA, Neoplasm / biosynthesis*
  • Escherichia coli
  • Female
  • Glutamine / pharmacology
  • Glycoproteins / metabolism
  • Humans
  • Melanoma / metabolism
  • Neoplasm Proteins / biosynthesis*
  • Pancreatic Neoplasms* / metabolism
  • RNA, Neoplasm / biosynthesis*
  • Vibrio

Substances

  • Amino Acids
  • DNA, Neoplasm
  • Glycoproteins
  • Neoplasm Proteins
  • RNA, Neoplasm
  • Glutamine
  • Asparagine
  • Asparaginase