Inhibition of pancreatic and lung adenocarcinoma cell survival by curcumin is associated with increased apoptosis, down-regulation of COX-2 and EGFR and inhibition of Erk1/2 activity

Shahar Lev-Ari, Alex Starr, Akiva Vexler, Vicki Karaush, Vered Loew, Joel Greif, Eyal Fenig, Dan Aderka, Rami Ben-Yosef

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Several studies suggested that curcumin inhibits growth of malignant cells via inhibition of cyclooxygenase-2 (COX-2) activity. Other studies indicated that epidermal growth factor receptor (EGFR) is also inhibited by curcumin in vitro and in vivo. Moreover, recent investigations revealed an intracellular cross-talk between EGFR signaling and the COX-2 pathway. Our aim was to evaluate whether the curcumin inhibitory effect on the survival of cancer cells is associated with simultaneous down-regulation of COX-2 and EGFR and inhibition of Erk1/2 (extra-cellular signal regulated kinase) signaling pathway. Materials and Methods: Lung and pancreas adenocarcinoma cell lines co-expressing COX-2 and EGFR (PC-14 and p34, respectively) and those expressing EGFR but deficient in COX-2 (H1299 and Panc-1, respectively) were exposed for 72 h to curcumin (0-50 μM). Cell viability was assessed by the XTT assay. Apoptosis was determined by FACS analysis. COX-2, EGFR, ErbB-2 and p-Erk1/2 expressions were measured by Western blot analysis. Results: Curcumin's inhibitory effect on survival and apoptosis of lung and pancreatic adenocarcinoma cell lines was significantly higher in the COX-2-expressing cells than in the COX-2-deficient cells. In the p34 and PC-14 cells, curcumin decreased COX-2, EGFR and p-Erk1/2 expressions in a dose-dependent manner. However, in the Panc-1 and H1299 cell lines, which did not express COX-2, curcumin did not affect EGFR levels. Conclusion: Curcumin co-inhibited COX-2 and EGFR expression and decreased Erk1/2 activity. This inhibition was associated with decreased survival and enhanced induction of apoptosis in lung and pancreatic adenocarcinoma cells.

Original languageEnglish
Pages (from-to)4423-4430
Number of pages8
JournalAnticancer Research
Volume26
Issue number6 B
StatePublished - Nov 2006

Keywords

  • COX-2
  • Curcumin
  • EGFR
  • Erk1/2
  • Non-small cell lung cancer
  • Pancreatic cancer

Fingerprint

Dive into the research topics of 'Inhibition of pancreatic and lung adenocarcinoma cell survival by curcumin is associated with increased apoptosis, down-regulation of COX-2 and EGFR and inhibition of Erk1/2 activity'. Together they form a unique fingerprint.

Cite this