RRC ID 17660
Author Hsum YW, Yew WT, Hong PL, Soo KK, Hoon LS, Chieng YC, Mooi LY.
Title Cancer chemopreventive activity of maslinic acid: suppression of COX-2 expression and inhibition of NF-κB and AP-1 activation in Raji cells.
Journal Planta Med.
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.
Volume 77(2)
Pages 152-7
Published 2011-1
DOI 10.1055/s-0030-1250203
PMID 20669087
MeSH 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*
IF 2.494
Times Cited 25
WOS Category INTEGRATIVE & COMPLEMENTARY MEDICINE CHEMISTRY, MEDICINAL PHARMACOLOGY & PHARMACY PLANT SCIENCES
Resource
Human and Animal Cells RAJI (RCB1647)