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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.
AuthorsPooi-Fong Wong, Wei-Fun Cheong, Meng-Hooi Shu, Chin-Hoe Teh, Kit-Lam Chan, Sazaly AbuBakar
JournalPhytomedicine : international journal of phytotherapy and phytopharmacology (Phytomedicine) Vol. 19 Issue 2 Pg. 138-44 (Jan 15 2012) ISSN: 1618-095X [Electronic] Germany
PMID21903368 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2011 Elsevier GmbH. All rights reserved.
Chemical References
  • Annexin A1
  • Antineoplastic Agents, Phytogenic
  • Biomarkers, Tumor
  • ERP29 protein, human
  • Heat-Shock Proteins
  • PHB protein, human
  • Plant Extracts
  • Prohibitins
  • Quassins
  • Repressor Proteins
  • Tumor Suppressor Protein p53
  • eurycomanone
  • Cisplatin
Topics
  • Annexin A1 (chemistry)
  • Antineoplastic Agents, Phytogenic (chemistry, pharmacology)
  • Biomarkers, Tumor (chemistry)
  • 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)
  • Prohibitins
  • Quassins (chemistry, isolation & purification, pharmacology)
  • Repressor Proteins (chemistry)
  • Tumor Stem Cell Assay
  • Tumor Suppressor Protein p53 (chemistry)

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