Eurycomanone suppresses expression of Lung Cancer Cell Tumor Markers, prohibitin, annexin 1 and endoplasmic reticulum protein 28

Wong, P.F.; Cheong, W.F.; Shu, M.H.; Teh, C.H.; Chan, K.L.; AbuBakar, S. (2012) Eurycomanone suppresses expression of Lung Cancer Cell Tumor Markers, prohibitin, annexin 1 and endoplasmic reticulum protein 28. Phytomedicine, 19 (2). pp. 138-144. ISSN 0944-7113

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    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 mu g/ml. The concentration that inhibited 50 of cell growth (GI(50)) was 5.1 mu g/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 mu g/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 mu g/ml to 15 mu g/ml with a GI(50) of 0.58 mu g/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 mu g/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. (C) 2011 Elsevier GmbH. All rights reserved.

    Item Type: Article
    1. Wong, P.F.
    2. Cheong, W.F.
    3. Shu, M.H.
    4. Teh, C.H.
    5. Chan, K.L.
    6. AbuBakar, S.( Department of Medical Microbiology, Faculty of Medicine Building, University of Malaya, 50603 Kuala Lumpur, Malaysia)
    Journal or Publication Title: Phytomedicine
    Additional Information: Wong, Pooi-Fong Cheong, Wei-Fun Shu, Meng-Hooi Teh, Chin-Hoe Chan, Kit-Lam AbuBakar, Sazaly
    Uncontrolled Keywords: Annexin A1/*chemistry Antineoplastic Agents, Phytogenic/chemistry/pharmacology Cell Line, Tumor Cell Proliferation/drug effects Cisplatin/pharmacology Dose-Response Relationship, Drug Electrophoresis, Gel, Two-Dimensional Eurycoma/chemistry Heat-Shock Proteins/*chemistry Humans Immunoblotting Lung Neoplasms/chemistry/*drug therapy Plant Extracts/chemistry/isolation & purification/*pharmacology Plant Roots/chemistry Quassins/chemistry/isolation & purification/*pharmacology Repressor Proteins/*chemistry Tumor Markers, Biological/*chemistry Tumor Stem Cell Assay Tumor Suppressor Protein p53/chemistry
    Subjects: R Medicine
    Divisions: Faculty of Medicine
    Depositing User: Miss Malisa Diana
    Date Deposited: 08 Nov 2012 10:08
    Last Modified: 08 Nov 2012 10:08

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