Taha, H. and Looi, C.Y. and Arya, A. and Wong, W.F. and Yap, L.F. and Hasanpourghadi, M. and Mohd, M.A. and Paterson, I.C. and Ali, H.M. (2015) (6E, 10E) Isopolycerasoidol and (6E, 10E) isopolycerasoidol methyl ester, prenylated benzopyran derivatives from pseuduvaria monticola induce mitochondrial-mediated apoptosis in human breast adenocarcinoma cells. PLoS ONE. ISSN 1932-6203, DOI https://doi.org/10.1371/journal.pone.0126126.
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Abstract
Phytochemicals from Pseuduvaria species have been reported to display a wide range of biological activities. In the present study, a known benzopyran derivative, (6E, 10E) isopolycerasoidol (1), and a new benzopyran derivative, (6E, 10E) isopolycerasoidol methyl ester (2), were isolated from a methanol extract of Pseuduvaria monticola leaves. The structures of the isolated compounds were elucidated by spectroscopic methods including 1D and 2D NMR, IR, UV, and LCMS-QTOF, and by comparison with previously published data. The anti-proliferative and cytotoxic effects of these compounds on human breast cancer cell-lines (MCF-7 and MDA-MB-231) and a human normal breast epithelial cell line (MCF-10A) were investigated. MTT results revealed both (1) and (2) were efficient in reducing cell viability of breast cancer cells. Flow cytometry analysis demonstrated that (1) and (2) induced cell death via apoptosis, as demonstrated by an increase in phosphotidylserine exposure. Both compounds elevated ROS production, leading to reduced mitochondrial membrane potential and increased plasma membrane permeability in breast cancer cells. These effects occurred concomitantly with a dose-dependent activation of caspase 3/7 and 9, a down-regulation of the anti-apoptotic gene BCL2 and the accumulation of p38 MAPK in the nucleus. Taken together, our data demonstrate that (1) and (2) induce intrinsic mitochondrial- mediated apoptosis in human breast cancer cells, which provides the first pharmacological evidence for their future development as anticancer agents.
| Item Type: | Article |
|---|---|
| Funders: | UNSPECIFIED |
| Additional Information: | This research is supported by a High Impact Research grant (UM-MOHE UM.C/625/1/HIR/MOHE/09), a University of Malaya research grant (RP001D-13BIO, RP027A-14HTM), and an IPS grant (PG064-2012B). The funders have no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. |
| Subjects: | R Medicine > RK Dentistry |
| Divisions: | Faculty of Dentistry |
| Depositing User: | Mr Ahmad Azwan Azman |
| Date Deposited: | 16 Jun 2015 08:07 |
| Last Modified: | 04 Jul 2017 01:14 |
| URI: | http://eprints.um.edu.my/id/eprint/13622 |
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