Nordin, Noraziah and Majid, Nazia Abdul and Othman, Rozana and Omer, Fatima Abdelmutaal Ahmed and Nasharuddin, Muhammad Nazil Afiq and Hashim, Najihah Mohd (2018) Plagioneurin B, a potent isolated compound induces apoptotic signalling pathways and cell cycle arrest in ovarian cancer cells. Apoptosis, 23 (2). pp. 152-169. ISSN 1360-8185, DOI https://doi.org/10.1007/s10495-018-1447-x.
Full text not available from this repository.Abstract
Plagioneurin B belongs to acetogenin group has well-established class of compounds. Acetogenin group has attracted worldwide attention in the past few years due their biological abilities as inhibitors for several types of tumour cells. Plagioneurin B was isolated via conventional chromatography and tested for thorough mechanistic apoptosis activity on human ovarian cancer cells (CAOV-3). Its structure was also docked at several possible targets using Autodock tools software. Our findings showed that plagioneurin B successfully inhibits the growth of CAOV-3 cells at IC 50 of 0.62 µM. The existence of apoptotic bodies, cell membrane blebbing and chromatin condensation indicated the hallmark of apoptosis. Increase of Annexin V-FITC bound to phosphatidylserine confirmed the apoptosis induction in the cells. The apoptosis event was triggered through the extrinsic and intrinsic pathways via activation of caspases 8 and 9, respectively. Stimulation of caspase 3 and the presence of DNA ladder suggested downstream apoptotic signalling were initiated. Further confirmation of apoptosis was conducted at the molecular levels where up-regulation in Bax, as well as down-regulation of Bcl-2, Hsp-70 and survivin were observed. Plagioneurin B was also seen to arrest CAOV-3 cells cycle at the G2/M phase. Docking simulation of plagioneurin B with CD95 demonstrated that the high binding affinity and hydrogen bonds formation may explain the capability of plagioneurin B to trigger apoptosis. This study is therefore importance in finding the effective compound that may offer an alternative drug for ovarian cancer treatment.
| Item Type: | Article |
|---|---|
| Funders: | Institute of Research Management and Monitory, University of Malaya under Flagship grant (FL001E-13BIO) |
| Uncontrolled Keywords: | Acetogenin; Apoptosis; CAOV-3 cells; Ovarian cancer; Pathways; Plagioneurin B |
| Subjects: | Q Science > Q Science (General) Q Science > QH Natural history R Medicine |
| Divisions: | Faculty of Medicine Faculty of Science > Institute of Biological Sciences |
| Depositing User: | Ms. Juhaida Abd Rahim |
| Date Deposited: | 30 Apr 2019 04:11 |
| Last Modified: | 30 Apr 2019 04:11 |
| URI: | http://eprints.um.edu.my/id/eprint/21106 |
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