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

• Published in: Planta medica Vol. 77; no. 2; p. 152
• Main Authors: Hsum, Yap Wei, Yew, Wong Teck, Hong, Paul Lim Vey, Soo, Khoo Kong, Hoon, Lim Saw, Chieng, Yeo Chew, Mooi, Lim Yang
• Format: Journal Article
• Language: English
• Published: Germany 01-01-2011
• Subjects: Anti-Inflammatory Agents - pharmacology; Anticarcinogenic Agents - pharmacology; Cell Line, Tumor; Cell Proliferation - drug effects; Cyclooxygenase 2 - drug effects; Cyclooxygenase 2 - metabolism; Electrophoretic Mobility Shift Assay; Gene Expression - drug effects; Humans; Lymphoma - metabolism; Lymphoma - pathology; Lymphoma - prevention & control; NF-kappa B - drug effects; NF-kappa B - metabolism; Oleanolic Acid - pharmacology; Signal Transduction; Transcription Factor AP-1 - drug effects; Transcription Factor AP-1 - metabolism; Triterpenes - chemistry; Triterpenes - pharmacology
• ISSN: 1439-0221
• DOI: 10.1055/s-0030-1250203

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.