Affordable Access

deepdyve-link
Publisher Website

Implication of NAG-1 in synergistic induction of apoptosis by combined treatment of sodium salicylate and PI3K/MEK1/2 inhibitors in A549 human lung adenocarcinoma cells

Authors
  • Kim, Cho Hee
  • Kim, Min Young
  • Moon, Ji Young
  • Hwang, Ji Won
  • Lee, Su Yeon
  • Joo, Young Mi
  • Han, Song Iy
  • Park, Hye Gyeong
  • Kang, Ho Sung
Type
Published Article
Journal
Biochemical Pharmacology
Publisher
Elsevier
Publication Date
Jan 01, 2008
Accepted Date
Feb 04, 2008
Volume
75
Issue
9
Pages
1751–1760
Identifiers
DOI: 10.1016/j.bcp.2008.02.002
Source
Elsevier
Keywords
License
Unknown

Abstract

Aspirin is used as chemopreventive agents in a variety of human cancer cells including those of colon, lung, breast, and leukemia. Sodium salicylate (NaSal, the natural deacetylated form of aspirin) induced cell cycle arrest and apoptosis in a dose-dependent manner in A549 cells; high dose (20 mM) of NaSal-induced apoptosis, whereas low dose (2–10 mM) induced cell cycle arrest. We found that NaSal-activated Akt/PKB, ERK1/2, and p38MAPK signal cascades. Twenty micromolar of NaSal-induced apoptotic response of A549 cells was enhanced by the PI3K inhibitors (LY294002 and wortmannin) and in a less extent by the MEK1/2 inhibitors (U0126 and PD98059), whereas it was suppressed by the p38MAPK inhibitor (SB203580). Furthermore, simultaneous inhibition of the Akt/PKB and ERK1/2 signal cascades could lower the dose of NaSal to induce apoptosis to 2 mM in A549 lung cancer cells. Similar enhancement was observed in cells treated with 2 mM NaSal and 100 μM genistein, an inhibitor of receptor tyrosine kinases (RTKs) that are upstream of PI3K and MEK1/2 signaling. We further demonstrated that NAG-1 plays a key role in apoptosis by NaSal-based combined treatment. Collectively, our findings indicate that inhibition of the pro-survival Akt/PKB and ERK1/2 signaling may increase the chemopreventive effects of NaSal and combined treatment of two natural compounds (NaSal and genistein) results in a highly synergistic induction of apoptosis, thereby increasing the chemopreventive effects of NaSal against cancer.

Report this publication

Statistics

Seen <100 times