The Concentration Factor Effect Study of Etoposide Drug and Annona squamosa L. Seeds Extracts on Topoisomerase II Inhibition Model: Catalytic Inhibitory and Interfacial Poisons

Authors

  • Naser Jawad Kadhim
  • Suad Gazi Jaafer AlKufi
  • Enas Hussein Ali
  • Dhifaf Zeki Aziz

DOI:

https://doi.org/10.37506/ijfmt.v15i2.15043

Keywords:

Etoposide, TOP2B, Custard apple, Poison, Suppressor.

Abstract

Background: Topoisomerase II plays an important role in cell proliferation and DNA regulation. It is
responsible for loosening the supercoiled form of DNA and for condensing chromosomes in eukaryotic cells.
Custard apple (Annona squamosa L.) (Annonaceae) has been one of the main ingredients of ethnomedical
preparation for the treatment of tumors in some countries, and has cytotoxic effects on cancerous cell lines.
Aim: assessment of Qualitative Inhibition (Catalytic Inhibitor or Interfacial Poisons) and Quantitative
(IC50%) of Custard apple Plant Seeds; Crude Extract (CCE) and Alkaloid Extract (CAE) of Human
Toposomerase IIA (TOP2A) compared to etoposide (VP-16) as a controlled drug. Methods: TOP2A (0.5
unit) and pHOT1 DNA plasmid (62.5ng), DNA plasmid relaxation assay required for inhibition testing.
Inhibitors, the seeds plant was extracted by 100% methanol for the preparation of crude with concentrations
(240, 160, 100, 80, 40, 20, and 10 µg/ml) and alkaloid (100, 80, 60, 40, 20, 10 and 5 µg/ml), and the VP-16
as a positive control drug (150, 100, 50, 25, 12.5, and 3.125 µg/ml). Results and Discussion: The CAE
showed a higher DNA plasmid relaxation inhibition, IC50% (27.46). The higher concentrations of CCE
and CAE play as a Catalytic Inhibitory Compounds CICs (as suppressor compound) rather than Interfacial
Poisons IFPs (as poisons compounds), quite the opposite at low concentrations. Higher concentrations may
inhibit the formation of the enzyme-DNA complex, resulting in the accumulation of the supercoiled form
of the DNA plasmid due to inactivation of the enzyme function. In comparison, at low concentrations of
inhibiting factors the linear structure is accumulated, which means that both strands cannot be rejoined.
Conclusions: The CAE had the highest inhibition activity on the TOPO2A compared to the other agents. In
contrast to the VP-16 drug, the CAE and CCE concentrations of this plant affected inhibition models.

Author Biographies

Naser Jawad Kadhim

Assistant Professor at University of Kufa, Faculty of Science, Department of Biology, Iraq

Suad Gazi Jaafer AlKufi

Lecturer at University
of Kufa, Faculty of Science. Iraq, Department of Pathological Analysis, Iraq

Enas Hussein Ali

Lecturer at university of Kufa,
Faculty of Science, Department of Biology, Iraq

Dhifaf Zeki Aziz

Lecturer at University
of Kufa, Faculty of Science. Iraq, Department of Pathological Analysis, Iraq

Published

2021-03-24

How to Cite

Naser Jawad Kadhim, Suad Gazi Jaafer AlKufi, Enas Hussein Ali, & Dhifaf Zeki Aziz. (2021). The Concentration Factor Effect Study of Etoposide Drug and Annona squamosa L. Seeds Extracts on Topoisomerase II Inhibition Model: Catalytic Inhibitory and Interfacial Poisons. Indian Journal of Forensic Medicine & Toxicology, 15(2), 4278-4288. https://doi.org/10.37506/ijfmt.v15i2.15043