Plagioneurin B, a potent isolated compound induces apoptotic signalling pathways and cell cycle arrest in ovarian cancer cells

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

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Official URL: https://doi.org/10.1007/s10495-018-1447-x

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
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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