Introduction ! Numerous phytochemicals from edible plants have been reported to interfere with specific stages of carcinogenesis [1]. Much effort has been directed towards the progressive search for novel chemopreventive agents from edible plants. Co- leus tuberosus Benth, also known as “ubi kemili” is an herbaceous plant which belongs to the fam- ily Lamiaceae. Its tubers are eaten as vegetables and pickles while the leaves of other Coleus spe- cies are used as spices [2]. Coleus tuberosus Benth has strong antitumor promoting properties [3]. One of the active antitumor promoting com- pounds in Coleus tuberosus tubers was identified as maslinic acid [4]. Maslinic acid (l " Fig. 1), a pen- tacyclic triterpene commonly present in medici- nal herbs, has antioxidant and antitumor prop- erties. Triterpenoids, which are synthesized in many plants by the cyclization of squalene, are widely used in Asian medicine [5]. They act at var- ious stages of tumor development to inhibit tu- mor initiation and promotion as well as to induce differentiation and apoptosis [6]. Prostaglandins are oxygenated-lipid signaling molecules formed from arachidonate and some other highly unsaturated fatty acids; they regu- late a wide variety of physiological processes, in- cluding blood clotting, wound healing, immune responses, bone metabolism, nerve growth and development, and inflammation [7]. The synthe- sis of prostaglandins is catalyzed by the cyclooxy- genase (COX) enzymes. COX-2, in particular, is the inducible form of COX, and COX-2 expression re- Abstract ! Chronic inflammation is one of the predisposing factors for neoplastic transformation. Targeting inflammation through suppression of the pro-in- flammatory pathway by dietary phytochemicals provides an important strategy for cancer preven- tion. Maslinic acid is a novel natural triterpenoid known to inhibit proliferation and induce apopto- sis in some tumor cell lines. Although maslinic acid has cytotoxic and pro-apoptotic effects on cancer cells, the underlying mechanisms of its ef- fects on the inflammatory pathway have yet to be elucidated. It has been reported that abnormal ex- pression of pro-inflammatory enzyme cyclooxy- genase-2 (COX-2) causes promotion of cellular proliferation, suppression of apoptosis, enhance- ment 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 transcrip- tional activation, were assessed using Raji cells. The anti-inflammatory action of maslinic acid was benchmarked against oleanolic acid and oth- er standard drugs. Western blot analysis and elec- trophoretic mobility shift assay (EMSA) were em- ployed 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 tri- terpenoid might be achieved, at least in part, via the NF-κB and AP-1 signaling pathways. Supporting information available online at http://www.thieme-connect.de/ejournals/toc/ plantamedica Cancer Chemopreventive Activity of Maslinic Acid: Suppression of COX-2 Expression and Inhibition of NF-κB and AP-1 Activation in Raji Cells Authors Yap Wei Hsum 1 , Wong Teck Yew 1 , Paul Lim Vey Hong 2 , Khoo Kong Soo 1 , Lim Saw Hoon 3 , Yeo Chew Chieng 4 , Lim Yang Mooi 1 Affiliations The affiliations are listed at the end of the article Key words l " Coleus tuberosus l " Lamiaceae l " maslinic acid l " cyclooxygenase‑2 (COX‑2) l " nuclear factor‑kappa B (NF‑κB) l " activator protein‑1 (AP‑1) received March 9, 2010 revised July 3, 2010 accepted July 6, 2010 Bibliography DOI http://dx.doi.org/ 10.1055/s-0030-1250203 Published online July 28, 2010 Planta Med 2011; 77: 152–157 © Georg Thieme Verlag KG Stuttgart · New York · ISSN 0032‑0943 Correspondence Dr. Lim Yang Mooi Faculty of Engineering and Science Universiti Tunku Abdul Rahman Kuala Lumpur Campus, Jalan Genting Kelang 53300 Setapak Kuala Lumpur Malaysia Phone: + 60 3 41 07 98 02 ext. 17 8 Fax: + 60 3 41 07 98 03 ymlim@utar.edu.my 152 Hsum YW et al. Cancer Chemopreventive Activity … Planta Med 2011; 77: 152–157 Original Papers