Apoptosis

, Volume 23, Issue 2, pp 152–169 | Cite as

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

  • Noraziah Nordin
  • Nazia Abdul Majid
  • Rozana Othman
  • Fatima Abdelmutaal Ahmed Omer
  • Muhammad Nazil Afiq Nasharuddin
  • Najihah Mohd Hashim
Original Paper

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 IC50 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.

Keywords

Plagioneurin B Acetogenin Ovarian cancer CAOV-3 cells Apoptosis Pathways 

Abbreviations

AIF

Apoptosis inducing factor

TRAIL-R

TNF-related apoptosis-inducing ligand-receptor

CD40L

CD40 ligand

SMAC

Second mitochondrial-derived activator of caspase

DR6

Death receptor 6

BID

BH3-interacting domain

BIM

Bcl-2-interacting mediator

FasL

Fas ligand

IGF

Insulin-like growth factor

IGFBP

Insulin-like growth factor binding protein

cIAP-2

Cellular inhibitor of apoptosis 2

TNF

Tumour necrosis factor

sTNFR

Soluble tumour necrosis factor receptor

HSP

Heat-shock proteins

XIAP

X chromosome-linked inhibitor of apoptosis

Notes

Acknowledgements

We wish to acknowledge the Institute of Research Management and Monitory, University of Malaya under Flagship grant (FL001E-13BIO) for their financial support. We also dedicate this study to the late Prof. Datuk Dr. A. Hamid A. Hadi for his guidance and assistance in this study.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Noraziah Nordin
    • 1
  • Nazia Abdul Majid
    • 2
  • Rozana Othman
    • 3
    • 4
  • Fatima Abdelmutaal Ahmed Omer
    • 3
  • Muhammad Nazil Afiq Nasharuddin
    • 5
  • Najihah Mohd Hashim
    • 3
    • 4
  1. 1.Medical Sciences 1, Faculty of Medicine & Health SciencesUniversiti Sains Islam MalaysiaKuala LumpurMalaysia
  2. 2.Institute of Biological Sciences, Faculty of ScienceUniversity of MalayaKuala LumpurMalaysia
  3. 3.Department of Pharmacy, Faculty of MedicineUniversity of MalayaKuala LumpurMalaysia
  4. 4.Center for Natural Products Research and Drug Discovery (CENAR)University of MalayaKuala LumpurMalaysia
  5. 5.Department of Chemistry, Faculty of ScienceUniversiti Putra MalaysiaSelangorMalaysia

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