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

Differential hepatic gene regulation in melanoma: Combined exercise and anti-inflammatory supplementation selectively lowers CXCL2 (murine IL-8 homolog) but not bFGF2

Articles in Press

Document Type : Original Article

Authors

Mahnaz Zarabadipour 1
Hossein Abednatanzi 2
Mandana Gholami 1

1 Department of physical education and sport sciences, SR.C., Islamic Azad university, Tehran, Iran.

2 Department of physical Education and Sport Science, Science and research branch, Islamic Azad University, Tehran, Iran.

10.22122/jeoct.2026.574951.1192
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.

What is already known on this subject?

It is well-established that the liver is a principal site for melanoma metastasis, and that the formation of a permissive pre-metastatic niche is driven by the upregulation of hepatic pro-inflammatory and pro-angiogenic factors, such as CXCL2/IL-8 HOMOLOG and bFGF2. Both structured aerobic exercise and anti-inflammatory dietary supplements, like bromelain from pineapple, have independently demonstrated potential to modulate systemic inflammation and cancer progression in various models.

 

What this study adds?

This study provides novel experimental evidence that a combined intervention of aerobic exercise and pineapple extract synergistically and selectively reduces the expression of hepatic CXCL2/IL-8 HOMOLOG, a master inflammatory chemokine, in melanoma-bearing mice, while having no significant effect on bFGF2. Furthermore, it reveals that this combined regimen, along with each individual intervention, disrupts the baseline negative correlation between CXCL2/IL-8 HOMOLOG and bFGF2 observed in untreated controls. These findings highlight the pathway-specific efficacy of non-pharmacological combinatorial strategies and advance our understanding of their potential to differentially rewire the molecular crosstalk within the hepatic pre-metastatic microenvironment.

Keywords

Melanoma
Liver
CXCL2/IL-8 HOMOLOG
bFGF2
Aerobic exercise
Pineapple extract
Gene expression
Murine model
Subjects

Acknowledgements

None.

Funding

None.

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 there is no conflict of interest in the present research.

Ethical approval All animal procedures were conducted in strict accordance with ethical guidelines for laboratory animal research and were approved by the institutional ethics committee of Islamic Azad University of Tehran (Iran).

Informed consent Animal study. 

Author contributions 

Conceptualization: M.Z., Methodology: M.Z., Software: M.Gh., Validation: H.A.,; Formal analysis: M.Z.,; Investigation: M.Z.,; Resources: M.Z.,; Data curation: H.A.,; Writing - original draft: M.Gh.,; Writing–review & editing M.Z.,; Visualization: H.A.,; Supervision: H.A.; Project administration: H.A.,.; Funding acquisition: M.Z.    

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Journal of Exercise & Organ Cross Talk

Articles in Press, Accepted Manuscript
Available Online from 01 June 2026

  • Receive Date 09 December 2025
  • Revise Date 21 February 2026
  • Accept Date 23 February 2026

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