Eurycomanone suppresses expression of Lung Cancer Cell Tumor Markers, prohibitin, annexin 1 and endoplasmic reticulum protein 28
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 gene...
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Format: | Article |
Language: | English |
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2012
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Online Access: | http://eprints.um.edu.my/3933/1/Wong-2012-Eurycomanone_suppres.pdf |
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author | Wong, P.F. Cheong, W.F. Shu, M.H. Teh, C.H. Chan, K.L. AbuBakar, Sazaly |
author_facet | Wong, P.F. Cheong, W.F. Shu, M.H. Teh, C.H. Chan, K.L. AbuBakar, Sazaly |
author_sort | Wong, P.F. |
collection | UM |
description | 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. |
first_indexed | 2024-03-06T05:10:59Z |
format | Article |
id | um.eprints-3933 |
institution | Universiti Malaya |
language | English |
last_indexed | 2024-03-06T05:10:59Z |
publishDate | 2012 |
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spelling | um.eprints-39332019-02-13T08:34:26Z http://eprints.um.edu.my/3933/ 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, Sazaly R Medicine 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. 2012 Article PeerReviewed application/pdf en http://eprints.um.edu.my/3933/1/Wong-2012-Eurycomanone_suppres.pdf Wong, P.F. and Cheong, W.F. and Shu, M.H. and Teh, C.H. and Chan, K.L. and AbuBakar, Sazaly (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, DOI https://doi.org/10.1016/j.phymed.2011.07.001 <https://doi.org/10.1016/j.phymed.2011.07.001>. http://ac.els-cdn.com/S0944711311002601/1-s2.0-S0944711311002601-main.pdf?_tid=5f5792e6-12b6-11e2-a104-00000aab0f6b&acdnat=1349858706_eeabc3e62daa042f5dba87c2acab3d70 10.1016/j.phymed.2011.07.001 |
spellingShingle | R Medicine Wong, P.F. Cheong, W.F. Shu, M.H. Teh, C.H. Chan, K.L. AbuBakar, Sazaly Eurycomanone suppresses expression of Lung Cancer Cell Tumor Markers, prohibitin, annexin 1 and endoplasmic reticulum protein 28 |
title | Eurycomanone suppresses expression of Lung Cancer Cell Tumor Markers, prohibitin, annexin 1 and endoplasmic reticulum protein 28 |
title_full | Eurycomanone suppresses expression of Lung Cancer Cell Tumor Markers, prohibitin, annexin 1 and endoplasmic reticulum protein 28 |
title_fullStr | Eurycomanone suppresses expression of Lung Cancer Cell Tumor Markers, prohibitin, annexin 1 and endoplasmic reticulum protein 28 |
title_full_unstemmed | Eurycomanone suppresses expression of Lung Cancer Cell Tumor Markers, prohibitin, annexin 1 and endoplasmic reticulum protein 28 |
title_short | Eurycomanone suppresses expression of Lung Cancer Cell Tumor Markers, prohibitin, annexin 1 and endoplasmic reticulum protein 28 |
title_sort | eurycomanone suppresses expression of lung cancer cell tumor markers prohibitin annexin 1 and endoplasmic reticulum protein 28 |
topic | R Medicine |
url | http://eprints.um.edu.my/3933/1/Wong-2012-Eurycomanone_suppres.pdf |
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