Leong, K.H. (2014) Subditine, a new monoterpenoid indole alkaloid from bark of nauclea subdita (Korth.) steud. induces apoptosis in human prostate cancer cells. PLoS ONE, 9 (2). e87286-e87286. ISSN 1932-6203, DOI https://doi.org/10.1371/journal.pone.0087286.
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Abstract
In this study, a new apoptotic monoterpenoid indole alkaloid, subditine (1), and four known compounds were isolated from the bark of Nauclea subdita. Complete 1H- and 13C- NMR data of the new compound were reported. The structures of isolated compounds were elucidated with various spectroscopic methods such as 1D- and 2D- NMR, IR, UV and LCMS. All five compounds were screened for cytotoxic activities on LNCaP and PC-3 human prostate cancer cell-lines. Among the five compounds, the new alkaloid, subditine (1), demonstrated the most potent cell growth inhibition activity and selective against LNCaP with an IC50 of 12.24±0.19 µM and PC-3 with an IC50 of 13.97±0.32 µM, compared to RWPE human normal epithelial cell line (IC50 = 30.48±0.08 µM). Subditine (1) treatment induced apoptosis in LNCaP and PC-3 as evidenced by increased cell permeability, disruption of cytoskeletal structures and increased nuclear fragmentation. In addition, subditine (1) enhanced intracellular reactive oxygen species (ROS) production, as reflected by increased expression of glutathione reductase (GR) to scavenge damaging free radicals in both prostate cancer cell-lines. Excessive ROS could lead to disruption of mitochondrial membrane potential (MMP), release of cytochrome c and subsequent caspase 9, 3/7 activation. Further Western blot analyses showed subditine (1) induced down-regulation of Bcl-2 and Bcl-xl expression, whereas p53 was up-regulated in LNCaP (p53-wild-type), but not in PC-3 (p53-null). Overall, our data demonstrated that the new compound subditine (1) exerts anti-proliferative effect on LNCaP and PC-3 human prostate cancer cells through induction of apoptosis.
| Item Type: | Article |
|---|---|
| Funders: | University of Malaya Research Grant RP001/2012 , University of Malaya High Impact Research Grant UM.C/625/1/HIR/MOHE/ SC/37 and HIR: E00002-20001, French National Center for Scientific Research CNRS grant 57-02-03-1007; , Postgraduate Research Funds of University of Malaya (PV050/2012A) |
| Uncontrolled Keywords: | Subditine, Monoterpenoid Indole Alkaloid, Nauclea subdita (Korth.) Steud., Caspase, Apoptosis, Human Prostate Cancer Cells. |
| Subjects: | Q Science > Q Science (General) Q Science > QD Chemistry Q Science > QH Natural history > QH301 Biology Q Science > QK Botany R Medicine R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) R Medicine > RM Therapeutics. Pharmacology R Medicine > RS Pharmacy and materia medica R Medicine > RV Botanic, Thomsonian, and eclectic medicine |
| Divisions: | Faculty of Medicine |
| Depositing User: | Dr. Leong Kok Hoong |
| Date Deposited: | 22 May 2014 02:06 |
| Last Modified: | 31 Jul 2018 04:22 |
| URI: | http://eprints.um.edu.my/id/eprint/10008 |
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