Cancer chemopreventive activity of maslinic acid: suppression of COX-2 expression and inhibition of NF-κB and AP-1 activation in Raji cells.
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.
Hsum
Yap Wei
YW
Department of Science, Faculty of Engineering & Science, Universiti Tunku Abdul Rahman, Kuala Lumpur, Malaysia.
Yew
Wong Teck
WT
Hong
Paul Lim Vey
PL
Soo
Khoo Kong
KK
Hoon
Lim Saw
LS
Chieng
Yeo Chew
YC
Mooi
Lim Yang
LY
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*
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