Journal of Exercise & Organ Cross Talk

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.

Abstract The aim of the present study is to investigate the effect of aerobic exercise and nano-curcumin supplementation on cardiac TGF-β1/TRAF6 and CTGF pathways in rat with brain tumors. Forty male Wistar rats were divided into 5 groups (n=8 in each) of healthy control, brain tumor, tumor + aerobic exercise (AE), tumor + nanocurcumin (N-CUR) and tumor+AE+N-CUR. Glioblastoma was injected into the rats in the frontal cortex. Nano curcumin supplement at the dose of 80 mg/kg was gavage for 4 weeks, 5 days a week. The training groups performed aerobic exercises on the treadmill for 4 weeks, 3 days a week at a speed of 18 meters per minute, for 25-40 minutes. At the end, the rats were sacrificed and TGF-β1, TRAF6, CTGF were analyzed from the myocardium by Real-time PCR method. Compared to the healthy control group, Tumor group significantly increased TGF-β1 mRNA and TRAF6 mRNA in the myocardium (p<0.05). Also, compared to the healthy control group, all tumor groups showed a significant increase in CTGF mRNA expression (p<0.05). In contrast to the Tumor group, the Tumor+AE and Tumor+AE+N-CUR groups showed a significant decrease in TGF-β1 mRNA at myocardium (p=0.0010 and p=0.0002, respectively). It seems that aerobic exercise or exercise with nano-curcumin supplement has better protective effects on the heart of tumor rats with downregulation of TGF-β1. It is suggested that different doses and various exercise modalities should be investigated to control cardiac fibrosis from the TGF-β1/TRAF6 and CTGF pathways.