PC-SPES down-regulates COX-2 via inhibition of NF-kappaB and C/EBPbeta in non-small cell lung cancer cells.

Abstract

Aberrant expression of COX-2 occurs in many types of malignancies including colon and lung cancers, and is implicated in development and progression of cancer. The molecular mechanisms associated with aberrant expression of COX-2 in lung cancer cells remain to be fully elucidated. In this study, we found that non-small cell lung cancer (NSCLC) NCI-H520 and NCI-H460 cells constitutively expressed COX-2 and produced prostaglandin E2 (PGE2) as measured by Western blotting and enzyme-linked immunosorbent assay (ELISA), respectively. Reporter assays showed that transcriptional regulation of COX-2 was blunted when either the NF-IL6 (C/EBPbeta) or nuclear factor-kappaB (NF-kappaB) binding site in the COX-2 promoter was mutated, suggesting that C/EBPbeta and NF-kappaB transcription factors have an important role in aberrant expression of COX-2 in these lung cancer cells. In addition, the eight herbal mixture PC-SPES (Lot. 5431219) caused growth arrest and apoptosis of NCI-H520 and NCI-H460 cells in association with blockade of NF-kappaB and down-regulation of C/EBPbeta, resulting in down-regulation of COX-2 and PGE2 in these cells. On the other hand, PC-SPES up-regulated the level of C/EBPbeta in these cells. Taken together, C/EBPbeta and NF-kappaB may be promising molecular targets for COX-2 inhibition in lung cancer cells. PC-SPES might be useful in the adjuvant setting for the treatment of individuals with resected NSCLC as well as other types of cancer in which COX-2 is activated.

• Authors: Takayuki Ikezoe, Yang Yang, Takayuki Saitoh, David Heber, Robert McKenna, Hirokuni Taguchi, H Phillip Koeffler
• Journal: International journal of oncology (Int J Oncol) Vol. 29 Issue 2 Pg. 453-61 (Aug 2006) ISSN: 1019-6439 [Print] Greece
• PMID: 16820889 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Phytogenic
• CCAAT-Enhancer-Binding Protein-beta
• Drugs, Chinese Herbal
• NF-kappa B
• herbal preparation PC-SPES

Topics

• Antineoplastic Agents, Phytogenic (pharmacology)
• Apoptosis
• Base Sequence
• CCAAT-Enhancer-Binding Protein-beta (metabolism)
• Cell Line, Tumor
• Down-Regulation
• Drugs, Chinese Herbal (pharmacology)
• Gene Expression Regulation, Enzymologic
• Gene Expression Regulation, Neoplastic
• Humans
• Lung Neoplasms (metabolism)
• Molecular Sequence Data
• NF-kappa B (metabolism)