Journal of Eexercise & Organ Cross Talk
Keywords = Melanoma
Cellular & Molecular Exercise Physiology

Differential hepatic gene regulation in melanoma: Combined exercise and anti-inflammatory supplementation selectively lowers CXCL2 but not bFGF2

Volume 6, Issue 2, Spring 2026, Pages 82-89

https://doi.org/10.22122/jeoct.2026.574951.1192

Mahnaz Zarabadipour, Hossein Abednatanzi, Mandana Gholami

Abstract Hepatic gene expression of inflammatory and growth factors such as IL-8 and bFGF2 may be modulated in melanoma metastasis. Non-pharmacological interventions like exercise and anti-inflammatory supplements represent potential complementary strategies for modification. This study aimed to investigate the effects of aerobic exercise, pineapple extract supplementation, and their combination on the hepatic expression of CXCL2/IL-8 HOMOLOG and bFGF2 genes in a murine melanoma model. Melanoma-bearing mice were allocated into four groups (n=5 per group): Control, Aerobic Exercise, Pineapple Extract Supplement, and Aerobic Exercise+Pineapple Extract. After the intervention period, liver tissue was analyzed for CXCL2/IL-8 HOMOLOG and bFGF2 gene expression via one-way ANOVA and Tukey HSD test. Pearson correlation assessed the relationship between the two genes. A significant difference was observed in CXCL2/IL-8 HOMOLOG gene expression between groups (F=4.211, p=0.0239). Post hoc analysis revealed that only the combined Aerobic Exercise + Pineapple Extract group showed a significant decrease in hepatic CXCL2/IL-8 HOMOLOG compared to the Cancer Control group (p=0.0251). In contrast, no significant difference was found in bFGF2 gene expression across groups (F=1.425, p=0.2745). Correlation analysis indicated a significant negative relationship between CXCL2/IL-8 HOMOLOG and bFGF2 exclusively in the Cancer Control group (r=-0.948, p=0.013). The combination of aerobic exercise and pineapple extract supplementation significantly reduces hepatic CXCL2/IL-8 HOMOLOG expression in melanoma-bearing mice, suggesting a potential synergistic effect in modulating the hepatic inflammatory microenvironment. The distinct lack of effect on bFGF2 and the specific negative correlation in controls highlight pathway-selective responses.

Cellular & Molecular Exercise Physiology

Modulatory effects of aerobic exercise and Urtica dioica hydroalcoholic extract on tumor growth and Interleukin-10 levels in a Murine melanoma model

Volume 6, Issue 2, Spring 2026, Pages 107-115

https://doi.org/10.22122/jeoct.2026.581673.1203

Saeed Sadeghi, Hossein Abednatanzi, Shahram Soheily

Abstract To investigate the individual and combined effects of six weeks of aerobic exercise and hydroalcoholic extract of Urtica dioica (nettle) on tumor volume, body weight, and interleukin-10 (IL-10) levels in both serum and tumor tissue in male C57BL/6 mice bearing B16F10 melanoma tumors. Thirty-two male C57BL/6 mice (6–8 weeks old, 12–14 g) were randomly assigned to four equal groups (n=8): Control, Aerobic Exercise (AE), Nettle Extract (NE), and Combined (AE+NE). Melanoma was induced via surgical implantation of B16F10 tumor fragments. The AE protocol consisted of treadmill running for 6 weeks (5 days/week, progressing from 20 to 30 minutes/session at 6–16 m/min). The NE group received intraperitoneal injections of hydroalcoholic nettle extract (200 mg/kg body weight). The combined group received both interventions. The combined AE+NE group showing a significant reduction in tumor volume compared to the control group (p=0.0186). One-way ANOVA revealed significant differences in serum IL-10 across groups (F=9.811, p=0.0001), with significant increases observed in the AE (p=0.0003) and AE+NE (p = 0.0005) groups compared to controls. For tumor IL-10, a significant difference was also found across groups (F=3.047, p= 0.0451), with the combined AE+NE group showing a significant decrease (p =0.0435) compared to the control group. No significant correlation was found between serum and tumor IL-10 levels in any group (p>0.05). The combined intervention significantly suppressed tumor growth compared to controls and was associated with increased serum IL-10 levels but decreased IL-10 levels within the tumor microenvironment, suggesting a complex, compartment-specific immunomodulatory effect.

Cellular & Molecular Exercise Physiology

The combined effects of resistance training and pineapple extract on intratumoral NF-κB, LIN28B, and systemic TNF-α in a murine melanoma model

Volume 5, Issue 3, Summer 2025, Pages 116-122

https://doi.org/10.22122/jeoct.2025.548128.1170

Adeleh Afshar, Hossein Abednatanzi, Farshad Ghazalian, Mandana Gholami

Abstract This study investigated the effects of resistance training and pineapple extract consumption on intratumoral NF-κB and LIN28B gene expression and serum TNF-α levels in a murine C57 melanoma model. Twenty C57BL/6 mice were allocated into four groups (n=5/group): melanoma tumor control (MT), MT with resistance training (MT+RT), MT with pineapple extract (MT+PJ), and MT with combined intervention (MT+RT+PJ). The RT protocol and PJ administration (300 mg/kg/day via gavage) were conducted for six weeks’ post-tumor induction. Serum TNF-α was quantified by ELISA, and tumor gene expression of NF-κB and LIN28B was analyzed via RT-PCR. Data were analyzed using one-way ANOVA followed by Tukey's post hoc test. All three intervention groups exhibited a significant downregulation of NF-κB and LIN28B gene expression in tumor tissue compared to the MT control group (p<0.05). Conversely, serum TNF-α levels were significantly elevated in the intervention groups relative to the control (p<0.05). Resistance training and pineapple extract consumption, both individually and in combination, significantly modulated pro-tumorigenic pathways by suppressing intratumoral NF-κB and LIN28B expression, despite an observed increase in systemic TNF-α.