title: Eurycomanone suppresses expression of lung cancer cell tumor markers, prohibitin, annexin 1 and endoplasmic reticulum protein 28.
abstract: Bioactive compounds from the medicinal plant, Eurycoma longifolia Jack have been shown to promote anti-proliferative effects on various cancer cell lines. Here we examined the effects of purified eurycomanone, a quassinoid found in Eurycoma longifolia Jack extract, on the expression of selected genes of the A549 lung cancer cells. Eurycomanone inhibited A549 lung cancer cell proliferation in a dose-dependent manner at concentrations ranging from 5 to 20 μg/ml. The concentration that inhibited 50% of cell growth (GI(50)) was 5.1 μg/ml. The anti-proliferative effects were not fully reversible following the removal of eurycomanone, in which 30% of cell inhibition still remained (p<0.0001, T-test). At 8 μg/ml (GI(70)), eurycomanone suppressed anchorage-independent growth of A549 cells by >25% (p<0.05, T-test, n=8) as determined using soft agar colony formation assay. Cisplatin, a chemotherapy drug used for the treatment of non small cell lung cancer on the other hand, inhibited A549 cells proliferation at concentrations ranging from 0.2 μg/ml to 15 μg/ml with a GI(50) of 0.58 μg/ml. The treatment with eurycomanone reduced the abundance expression of the lung cancer markers, heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1, p53 tumor suppressor protein and other cancer-associated genes including prohibitin (PHB), annexin 1 (ANX1) and endoplasmic reticulum protein 28 (ERp28) but not the house keeping genes. The mRNA expressions of all genes with the exception of PHB were significantly downregulated, 72 h after treatment (p<0.05, T-test, n=9). These findings suggest that eurycomanone at viable therapeutic concentrations of 5-20 μg/ml exhibited significant anti-proliferative and anti-clonogenic cell growth effects on A549 lung cancer cells. The treatment also resulted in suppression of the lung cancer cell tumor markers and several known cancer cell growth-associated genes.
authors: Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors: Pooi-Fong
authors: PF
authors: Wong
authors: Wei-Fun
authors: WF
authors: Cheong
authors: Meng-Hooi
authors: MH
authors: Shu
authors: Chin-Hoe
authors: CH
authors: Teh
authors: Kit-Lam
authors: KL
authors: Chan
authors: Sazaly
authors: S
authors: AbuBakar
mesh_terms: D017305:Annexin A1 / Q000737:chemistry*; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000737:chemistry*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015180:Electrophoresis, Gel, Two-Dimensional; D035701:Eurycoma / Q000737:chemistry; D006360:Heat-Shock Proteins / Q000737:chemistry*; D006801:Humans; D015151:Immunoblotting; D008175:Lung Neoplasms / Q000737:chemistry / Q000188:drug therapy*; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D018517:Plant Roots / Q000737:chemistry; D000091402:Prohibitins; D036702:Quassins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D012097:Repressor Proteins / Q000737:chemistry*; D014410:Tumor Stem Cell Assay; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry
chemical_list: D017305:Annexin A1; D000972:Antineoplastic Agents, Phytogenic; D014408:Biomarkers, Tumor; C491738:ERP29 protein, human; D006360:Heat-Shock Proteins; C000717328:PHB protein, human; D010936:Plant Extracts; D000091402:Prohibitins; D036702:Quassins; D012097:Repressor Proteins; D016159:Tumor Suppressor Protein p53; C506425:eurycomanone; D002945:Cisplatin