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Effect of pharmacodynamical interaction between nutlin-3a and aspirin in the activation of p53

Muhammad Suleman Awan1, Maria Aslam1, Muwahida Liaquat1

  • 1Department of Electrical Engineering, National University of Sciences and Technology, Islamabad, Pakistan.

Journal of Theoretical Biology
|April 1, 2021
PubMed
Abstract

Insights

Nutlin-3a activates anti-tumor protein p53. Combining it with a low dose of aspirin shows no harmful drug interactions. However, a high dose of aspirin causes over-expression of p53, potentially harming healthy cells.

Area of Science:

  • Oncology
  • Pharmacology
  • Control Systems Engineering

Background:

  • The anti-tumor protein p53 is inactivated in most cancers.
  • Nutlin-3a activates p53 by inhibiting Mdm2.
  • Cancer patients face high risks of drug-drug interactions (DDIs) from polypharmacy.

Purpose of the Study:

  • To investigate the pharmacodynamical interaction between nutlin-3a and aspirin in p53 protein activation.
  • To assess the safety and efficacy of combined anti-cancer drug regimens.

Main Methods:

  • Utilized control system techniques to design a Proportional-Integral-Derivative (PID) controller for p53 activation.
  • Incorporated a drug interaction parameter to model the combined effects of nutlin-3a and aspirin.
  • Conducted extensive simulations using both low and high doses of aspirin.

Main Results:

  • No adverse pharmacodynamical interactions were observed when nutlin-3a was combined with a low dose of aspirin.
  • A high dose of aspirin acted as an input disturbance, leading to undesirable p53 over-expression.
  • Comparative analysis indicated that nutlin-3a with low-dose aspirin is superior to high-dose aspirin for p53 activation.

Conclusions:

  • The study provides insights into p53 activation dynamics under pharmacodynamical interactions.
  • Findings suggest that combining nutlin-3a with low-dose aspirin may be a safer and more effective cancer treatment strategy.
  • This research could aid in the effective management of cancer patients undergoing combination therapy.
Keywords:
DDIsMdm2 proteinPIDPharmacodynamical interactionp53 protein

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