Journal of Exercise & Organ Cross Talk
Journal of Eexercise & Organ Cross Talk

Resistance training and nanocurcumin modulate the p53 pathway in glioblastoma: Implications for inter-organ cross-talk

Document Type : Original Article

Authors

Reza Rostami 1
Parvin Farzanegi 2
Masoumeh Hosseini 3
Shahin Riyahi Malayeri 3
Hossein Shirvani 4

1 Department of Physical Education and Sport Sciences, NT.C., Islamic Azad University, Tehran, Iran.

2 Department of Physical Education and Sport Sciences, S.C., Islamic Azad University, Sari, Iran.

3 Department of Physical Education and Sport Sciences, ET.C., Islamic Azad University, Tehran, Iran.

4 Exercise Physiology Research Center, Life style Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran.

https://doi.org/10.22122/jeoct.2025.539985.1164
Abstract
Glioblastoma multiforme (GBM) exhibits dysregulated p53 tumor-suppressor signaling, driving therapeutic resistance; exercise and nutraceuticals represent promising adjuvants for pathway modulation. This study investigated resistance training and nanocurcumin in an orthotopic GBM rat model (n=40), with groups including healthy controls, cancer controls, nanocurcumin (80 mg/kg/day), resistance training (ladder climbing, 50% BW + 30g, 3×/week), and combined intervention. After 4 weeks, tumor tissue analysis revealed resistance training significantly reduced p53 mRNA expression versus cancer controls (1.8 ± 0.2 vs. 3.1 ± 0.3; p = 0.021), while all interventions suppressed p21 (combination group: 1.2 ± 0.1 vs. control 4.0 ± 0.4; p < 0.001), demonstrating 70% greater p21 inhibition in the combined group versus monotherapies (p < 0.01). The synergistic p21 downregulation indicates potent disruption of the G1/S cell-cycle checkpoint, likely mediated through inter-organ cross-talk along the muscle-liver-brain axis—where exercise-induced myokines (IL-6, BDNF) mitigate tumor oxidative stress, nanocurcumin suppresses hepatic inflammatory mediators, and hemodynamic adaptations enhance blood-brain barrier penetration. These findings position resistance training and nanocurcumin as a novel non-pharmacological adjuvant strategy to potentiate conventional glioma therapies by leveraging systemic physiological communication.

What is already known on this subject?

Glioblastoma multiforme (GBM) exhibits dysregulated p53 tumor-suppressor signaling, driving therapeutic resistance; exercise and nutraceuticals represent promising adjuvants for pathway modulation.

 

What this study adds?

combined resistance training and nanocurcumin administration exerts synergistic inhibition of p21 expression in glioblastoma, surpassing the effects of either intervention alone.

Keywords

Glioblastoma
P53 signaling
Resistance training
Nanocurcumin
Inter-organ cross-talk
Synergistic effect
Adjuvant therapy

Subjects

Acknowledgements

None

Funding

No sources of funding were sought or awarded for this study.

Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Compliance with ethical standards

Conflict of interest The authors declare that they have no conflict of interest.

Ethical approval Ethical principles of working with laboratory animals based on the Declaration of Helsinki.

Informed consent Animal study.

Author contributions

Conceptualization: R.R, P.F,; Methodology: H.Sh, M.H,;  Software: Sh.RM,; Validation: P.F,; Formal analysis: R.R,; Investigation: M.H,;   Resources: H.Sh,; Data curation: R.R,; Writing - original draft: M.H,; Writing - review & editing: R.R,; Visualization: Sh.RM,;  Supervision: P.F,; Project administration: Sh.RM,; Funding acquisition: P.F.  

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Journal of Exercise & Organ Cross Talk
Volume 5, Issue 2
Spring 2025
Pages 91-95

  • Receive Date 07 March 2025
  • Revise Date 10 June 2025
  • Accept Date 19 June 2025

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