S-Adenosyl-l-Methionine Overcomes uL3-Mediated Drug Resistance in p53 Deleted Colon Cancer Cells

Int J Mol Sci. 2020 Dec 24;22(1):103. doi: 10.3390/ijms22010103.

Abstract

Purpose: In order to study novel therapeutic approaches taking advantage of natural compounds showing anticancer and anti-proliferative effects, we focused our interest on S-adenosyl-l-methionine, a naturally occurring sulfur-containing nucleoside synthesized from adenosine triphosphate and methionine by methionine adenosyltransferase, and its potential in overcoming drug resistance in colon cancer cells devoid of p53.

Results: In the present study, we demonstrated that S-adenosyl-l-methionine overcomes uL3-mediated drug resistance in p53 deleted colon cancer cells. In particular, we demonstrated that S-adenosyl-l-methionine causes cell cycle arrest at the S phase; inhibits autophagy; augments reactive oxygen species; and induces apoptosis in these cancer cells.

Conclusions: Results reported in this paper led us to propose S-adenosyl-l-methionine as a potential promising agent for cancer therapy by examining p53 and uL3 profiles in tumors to yield a better clinical outcomes.

Keywords: AdoMet; apoptosis; autophagy; colon cancer; drug resistance; uL3.

MeSH terms

  • Colonic Neoplasms* / drug therapy
  • Colonic Neoplasms* / genetics
  • Colonic Neoplasms* / metabolism
  • Drug Resistance, Neoplasm / drug effects*
  • Drug Resistance, Neoplasm / genetics
  • Gene Deletion*
  • HCT116 Cells
  • Humans
  • Ribosomal Protein L3
  • Ribosomal Proteins / genetics
  • Ribosomal Proteins / metabolism*
  • S-Adenosylmethionine / pharmacology*
  • Tumor Suppressor Protein p53 / deficiency*
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • RPL3 protein, human
  • Ribosomal Protein L3
  • Ribosomal Proteins
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • S-Adenosylmethionine