title: 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.affiliation: Department of Science, Faculty of Engineering & Science, Universiti Tunku Abdul Rahman, Kuala Lumpur, Malaysia.
authors.forename: Yap Wei
authors.initials: YW
authors.lastname: Hsum
authors.forename: Wong Teck
authors.initials: WT
authors.lastname: Yew
authors.forename: Paul Lim Vey
authors.initials: PL
authors.lastname: Hong
authors.forename: Khoo Kong
authors.initials: KK
authors.lastname: Soo
authors.forename: Lim Saw
authors.initials: LS
authors.lastname: Hoon
authors.forename: Yeo Chew
authors.initials: YC
authors.lastname: Chieng
authors.forename: Lim Yang
authors.initials: LY
authors.lastname: Mooi
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000187:drug effects* / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008223:Lymphoma / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D016328:NF-kappa B / Q000187:drug effects* / Q000378:metabolism; D009828:Oleanolic Acid / Q000494:pharmacology / Q000031:analogs & derivatives; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000187:drug effects* / Q000378:metabolism; D014315:Triterpenes / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D016588:Anticarcinogenic Agents; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D014315:Triterpenes; D009828:Oleanolic Acid; C412811:maslinic acid; D051546:Cyclooxygenase 2