Cancer chemopreventive activity of maslinic acid: suppression of COX-2 expression and inhibition of NF-κB and AP-1 activation in Raji cells.

Abstract

Chronic inflammation is one of the predisposing factors for neoplastic transformation. Targeting inflammation through suppression of the pro-inflammatory pathway by dietary phytochemicals provides an important strategy for cancer prevention. Maslinic acid is a novel natural triterpenoid known to inhibit proliferation and induce apoptosis in some tumor cell lines. Although maslinic acid has cytotoxic and pro-apoptotic effects on cancer cells, the underlying mechanisms of its effects on the inflammatory pathway have yet to be elucidated. It has been reported that abnormal expression of pro-inflammatory enzyme cyclooxygenase-2 (COX-2) causes promotion of cellular proliferation, suppression of apoptosis, enhancement of angiogenesis and invasiveness. In the present study, the suppressive effect of maslinic acid on COX-2 expression and the binding activity of upstream transcription factors NF- κB and AP-1, which are known to regulate COX-2 transcriptional activation, were assessed using Raji cells. The anti-inflammatory action of maslinic acid was benchmarked against oleanolic acid and other standard drugs. Western blot analysis and electrophoretic mobility shift assay (EMSA) were employed to analyze COX-2 expression as well as NF- κB and AP-1 binding activity. Our results showed that maslinic acid suppresses COX-2 expression in a concentration-dependent manner. Likewise, the constitutive nuclear NF- κB (p65) activity as well as phorbol 12-myristate 13-acetate (PMA)- and sodium N-butyrate (SnB)-induced AP-1 binding activity in Raji cells were significantly reduced following treatment with maslinic acid. Since maslinic acid suppresses COX-2 expression in Raji cells at concentrations that also lowered the NF- κB (p65) and AP-1 binding activity, it is possible that the suppression of COX-2 by this natural triterpenoid might be achieved, at least in part, via the NF- κB and AP-1 signaling pathways.

• Authors: Yap Wei Hsum, Wong Teck Yew, Paul Lim Vey Hong, Khoo Kong Soo, Lim Saw Hoon, Yeo Chew Chieng, Lim Yang Mooi
• Journal: Planta medica (Planta Med) Vol. 77 Issue 2 Pg. 152-7 (Jan 2011) ISSN: 1439-0221 [Electronic] Germany
• PMID: 20669087 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © Georg Thieme Verlag KG Stuttgart · New York.

Chemical References

• Anti-Inflammatory Agents
• Anticarcinogenic Agents
• NF-kappa B
• Transcription Factor AP-1
• Triterpenes
• Oleanolic Acid
• maslinic acid
• Cyclooxygenase 2

Topics

• Anti-Inflammatory Agents (pharmacology)
• Anticarcinogenic Agents (pharmacology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cyclooxygenase 2 (drug effects, metabolism)
• Electrophoretic Mobility Shift Assay
• Gene Expression (drug effects)
• Humans
• Lymphoma (metabolism, pathology, prevention & control)
• NF-kappa B (drug effects, metabolism)
• Oleanolic Acid (pharmacology)
• Signal Transduction
• Transcription Factor AP-1 (drug effects, metabolism)
• Triterpenes (chemistry, pharmacology)