The effect of aerobic exercise training on the expression of genes involved in cardiac apoptosis (Caspase-3/-7) in rats with glioblastoma multiforme

Document Type : Original Article


1 Ph.d.student of Department of Physical Education and Sport Science, Science and Research Branch, Islamic Azad University, Tehran, Iran.

2 Department of Physical Education and Sport Science, Science and Research Branch, Islamic Azad University, Tehran, Iran.

3 Exercise Physiology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.


Performing aerobic exercise in different disease conditions can regulate cardiac homeostasis and reduce cardiac apoptosis caused by the disease. In brain cancer, other tissues, including cardiac tissue, can also be affected. Since exercise training causes organ crosstalk, in this study, the effects of aerobic exercise training (AET) on cardiac apoptosis in Glioblastoma multiforme (GBM) rats are evaluated. Twenty-four male Wistar rats were divided into 3 groups (n=8 in each) of healthy control, GBM, and GBM+AET. Glioblastoma was injected into the frontal cortex of rats. The training group (AET) 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. In the end, the rats were sacrificed and caspase-3 and caspase-7 were analyzed from the myocardium by Real-time PCR method. Considering H&E image, the GBM group showed necrosis and apoptosis in cardiac tissue compared to the healthy group. Compared to the healthy control group, GBM significantly increased caspase-3 and caspase-7 mRNA in the myocardium (p<0.05). However, in contrast to the GBM group, the GBM+AET showed a significant decrease in caspase-3 and caspase-7 mRNA at the myocardium (p<0.05). Since tumor formation in the body can affect other distant tissues in an endocrine manner, it is suggested to prioritize aerobic exercise to control the damage caused by GBM on heart tissue. However, more studies are needed, especially on human samples.

What is already known on this subject?

Performing aerobic exercise in different disease conditions can regulate cardiac homeostasis and reduce cardiac apoptosis caused by the disease.


What this study adds?

Doing light aerobic exercise even for a short period can prevent these types of injuries.


Main Subjects


I hereby thank everyone who has helped me in this research.


There is no funding to report.

Compliance with ethical standards

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

Ethical approval The study was approved by the Ethics Committee of the Islamic Azad University, Tehran, Iran under protocol number IR.IAU.SRB.REC.1401.029.

Informed consent Animal study.

Author contributions

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

Al-Jarrah, M., Matalka, I., Al Aseri, H., Mohtaseb, A., Smirnova, I. V., Novikova, L., . . . AlKhateeb, A. (2010). Exercise training prevents endometrial hyperplasia and biomarkers for endometrial cancer in rat model of type 1 diabetes. Journal of clinical medicine research, 2(5), 207. doi:
Arabzadeh, E., Norouzi Kamareh, M., Ramirez‐Campillo, R., Mirnejad, R., Masti, Y., & Shirvani, H. (2022). Twelve weeks of treadmill exercise training with green tea extract reduces myocardial oxidative stress and alleviates cardiomyocyte apoptosis in aging rat: The emerging role of BNIP3 and HIF‐1α/IGFBP3 pathway. Journal of Food Biochemistry, 46(12), e14397. doi:
Asadi, M., Taghizadeh, S., Kaviani, E., Vakili, O., Taheri‐Anganeh, M., Tahamtan, M., & Savardashtaki, A. (2022). Caspase‐3: structure, function, and biotechnological aspects. Biotechnology and Applied Biochemistry, 69(4), 1633-1645. doi:
Chiang, S.-L., Heitkemper, M. M., Hung, Y.-J., Tzeng, W.-C., Lee, M.-S., & Lin, C.-H. (2019). Effects of a 12-week moderate-intensity exercise training on blood glucose response in patients with type 2 diabetes: A prospective longitudinal study. Medicine, 98(36). doi:
Farinha, J. B., Steckling, F. M., Stefanello, S. T., Cardoso, M. S., Nunes, L. S., Barcelos, R. P., . . . Bresciani, G. (2015). Response of oxidative stress and inflammatory biomarkers to a 12-week aerobic exercise training in women with metabolic syndrome. Sports medicine-open, 1(1), 1-10. doi:
Ge, Z., & Ding, S. (2020). The crosstalk between tumor-associated macrophages (TAMs) and tumor cells and the corresponding targeted therapy. Frontiers in oncology, 10, 590941. doi:
Gremeaux, V., Gayda, M., Lepers, R., Sosner, P., Juneau, M., & Nigam, A. (2012). Exercise and longevity. Maturitas, 73(4), 312-317. doi:
Hofmann, K. (1999). The modular nature of apoptotic signaling proteins. Cellular and Molecular Life Sciences CMLS, 55, 1113-1128. doi:
Hosseini, F., Hassannia, H., Mahdian‐Shakib, A., Jadidi‐Niaragh, F., Enderami, S. E., Fattahi, M., . . . Kokhaei, P. (2017). Targeting of crosstalk between tumor and tumor microenvironment by β‐D mannuronic acid (M2000) in murine breast cancer model. Cancer medicine, 6(3), 640-650. doi:
Ji, L. L. (1999). Antioxidants and oxidative stress in exercise. Proceedings of the Society for experimental Biology and Medicine, 222(3), 283-292. doi:
Kumar, S. (1999). Mechanisms mediating caspase activation in cell death. Cell Death & Differentiation, 6(11), 1060-1066. doi:
Kwak, H.-B. (2013). Effects of aging and exercise training on apoptosis in the heart. Journal of exercise rehabilitation, 9(2), 212. doi:
Livak, K. J., & Schmittgen, T. D. (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2− ΔΔCT method. methods, 25(4), 402-408. doi:
McComb, S., Chan, P. K., Guinot, A., Hartmannsdottir, H., Jenni, S., Dobay, M. P., . . . Bornhauser, B. C. (2019). Efficient apoptosis requires feedback amplification of upstream apoptotic signals by effector caspase-3 or-7. Science advances, 5(7), eaau9433. doi:
Morton, J. P., Kayani, A. C., McArdle, A., & Drust, B. (2009). The exercise-induced stress response of skeletal muscle, with specific emphasis on humans. Sports Medicine, 39, 643-662. doi:
Ostrom, Q. T., Gittleman, H., Fulop, J., Liu, M., Blanda, R., Kromer, C., . . . Barnholtz-Sloan, J. S. (2015). CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2008-2012. Neuro-oncology, 17(suppl_4), iv1-iv62. doi:
Sharif, P. M., Khoshbin, A. P., Nasrollahzadeh, E., Keshavarz-Fathi, M., & Rezaei, N. (2023). Tumor immunology. In Clinical Immunology (pp. 245-452). Elsevier.
Swanson, L. W. (2018). Brain maps 4.0—Structure of the rat brain: An open access atlas with global nervous system nomenclature ontology and flatmaps. Journal of Comparative Neurology, 526(6), 935-943. doi:
Zhang, J. (2003). Zhang Y, Herman B. Caspases, apoptosis and aging. Ageing Res Rev, 2, 357-366. doi: