Volume 29, Issue 9 (12-2022)
RJMS 2022, 29(9): 216-226 |
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Research code: IR.IAU.M.REC.1399.008
Ethics code: IR.IAU.M.REC.1399.008
Clinical trials code: نویسندگان متعهد می شوند که کد اخلاق در زمان چاپ مقاله ا
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Firoozi M, Barari A, Abbassi Daloii A, Abednatanzi H. The Effect of Interval Training and Consumption of Urtica dioica Hydroalcoholic Extract on Heat Shock Protein 70 and Extracellular Matrix Metalloproteinase Inducer in C57 Rats with Melanoma Cancer. RJMS 2022; 29 (9) :216-226
URL: http://rjms.iums.ac.ir/article-1-7640-en.html
URL: http://rjms.iums.ac.ir/article-1-7640-en.html
Associate Professor, Department of Exercise Physiology, Ayatollah Amoli Branch, Islamic Azad University, Amol, Iran , alireza54.barari@gmail.com
Abstract: (1177 Views)
Background & Aims: Melanoma, caused by gene mutations of melanocytes, is the most aggressive skin cancer (1). The pathogenesis of melanoma is complex and involves genetic and environmental factors. The increased incidence of melanoma in developed countries is mostly due to excessive exposure to sunlight (ultraviolet light), which is the main risk factor for cutaneous melanoma (2). The interaction of melanoma cells with other cells residing in the tumor microenvironment significantly affects tumor biology such as proliferation, differentiation, and growth (3). Collective action of molecular chaperones is also necessary to maintain cellular homeostasis leading to survival (4). In human cells, stress-induced Hsp70 is expressed in the cytosol of many tumors, where it performs a wide variety of chaperone functions such as folding-unfolding and translocation of polypeptides across cell membranes, cloning and dissociation of protein complexes, and regulation of protein activity (5). High expression of Hsp70 is associated with tumor initiation, progression and survival in various types of cancer (7,8). Molecular studies show that subunits of the HSP70 protein family reduce the stability of extracellular matrix metalloproteinase-inducible protein (CD147) by increasing ubiquitin-proteasome degradation, thereby inhibiting lactate and glycolysis, and ultimately metastasis and cell migration (9). On the other hand, the tendency of melanoma cells to invade distant tissues depends on their interaction with tumor microenvironment cells and the efficiency of the immune response (10). CD147, also known as Basigin, is a highly glycosylated type I membrane protein of the large family of immunoglobulins (11). A previous study has shown that CD147 plays a key role in cell apoptosis (12).
In recent years, due to fewer side effects of herbal medicines, the use of plant-derived compounds as anti-cancer drugs has increased significantly. Clinical studies show that nettle species contain compounds that show activity against cancer cells (16,17). Exercise can also reduce the risk of cancer by changing the response of immune factors (18). Wennerberg et al. (2020) found in a breast cancer model that incorporating 30 minutes of treadmill running five days per week during the anti-PD-1/radiotherapy course reduced tumor-infiltrating myeloid-derived suppressor cells and increased the infiltration of tumor cells. becomes CD8+ T, which is more useful for the function of immune cells (19). However, in Crosby et al.'s (2021) research, there was no statistically significant change in quality of life, fatigue, physical performance, cardiorespiratory fitness, body composition, psychological distress, cognitive performance, or treatment-related side effects compared to physical activity or exercise (20). Previous reports have shown the antitumor activity of nettle in various human malignancies, such as breast, lung, and prostate cancers (17,22). However, despite the therapeutic benefits of nettle plant, the effects of nettle extract on changes in immune and growth factors in melanoma cancer are not clear. Considering the therapeutic benefits of nettle plant as well as the positive effect of exercise in reducing the effect of interval training and consumption of Urtica dioica hydroalcoholic extract on Heat shock protein 70 (HSP70) and Extracellular matrix metalloproteinase inducer (CD147) in C57 rats with melanoma cancer.
Methods: In this experimental study, 20 C57 rats were randomly divided into four groups include control (cancer), Urtica dioica (cancer), and Urtica dioica - interval training (cancer). One week after the induction of melanoma cancer, the experimental group consumed 30 mg/kg/day nettle ethanol extract orally for 8 weeks. The interval exercise program included running on a treadmill 60 minutes at a speed of 28 meters per minute, five days a week for six weeks. The HSP70 and CD147 ranks were measured by Real time PCR. The data were analyzed and analyzed by One -way variance analysis and the Toky's test at the p<0.05.
Results: The results showed that interval training, Urtica dioica hydroalcoholic extract and interval training with Urtica dioica hydroalcoholic extract consumption led to significant increase in the amount of HSP70 and significant decrease in the amount of CD147 in C57 rats with melanoma cancer (P<0.001).
Conclusion: The findings of the present research show that interval training led to a significant increase in the level of heat shock protein 70 and a significant decrease in the level of extracellular matrix metalloproteinase inducer in C57 mice with melanoma cancer. The findings of the present research are consistent with some results of previous studies (19,25). HSP70 induction depends on exercise intensity. High-intensity exercise has a greater effect on stimulating heat shock reactions (26). It seems that one of the effective mechanisms of exercise training on the levels of heat shock proteins is the increase in body temperature and the occurrence of oxidative stress during physical activity, which can be the reason for the increase of these markers after exercise. One of the important mechanisms of CD147 effect in promoting cancer metastasis is the metabolic regulation of the tumor microenvironment through interaction with specific MCTs, such as MCT4, which helps to facilitate lactate transport and tumor glycolysis (29,30). Little is known about the regulation of heat shock proteins in CD147 expression. In one study, it was shown that the reduction of the HSP70 protein family was associated with the increase of CD147 protein expression in human cancer cell tumors, suggesting that the negative regulation of the HSP70 protein family maybe It can increase the migration of cancer cells by upregulating CD147. This hypothesis is supported by findings that the HSP70 protein family negatively regulates the abundance and membrane expression of CD147 protein in cancer cells (9). Also, the results of our study show that nettle hydroalcoholic consumption led to a significant increase in the level of heat shock protein 70 and a significant decrease in the level of extracellular matrix metalloproteinase inducer in C57 mice with melanoma cancer. Stinging nettle extract may exert biological anticancer activities through various mechanisms, including antioxidant and antimutagenic properties, induction or inhibition of key processes in cellular metabolism, and the ability to activate apoptotic pathways (17). The most likely explanation for the significant anticancer effect of nettle is its content of flavonoids and other known molecules and/or as yet unknown substances. In addition, the findings of our study show that interval training with the consumption of nettle hydroalcoholic significantly led to a further decrease in the level of extracellular matrix metalloproteinase inducer in C57 mice with melanoma cancer. Therefore, it is possible that intermittent exercises in combination with nettle hydroalcoholic consumption may lead to a more effective regulation of immune factors in melanoma cancer, but a definitive statement requires more research in this field. The main strength of the present study is to compare the effectiveness of several interventions to identify the best intervention. The current approach results in more informed decisions. There were also limitations in the present research, among which we can point out the small number of samples in the present research, therefore, a similar study with the measurement of these indicators in a high number of samples is suggested. It is also suggested that similar research be done by measuring immune growth factors following other exercise protocols. The results of the present study showed that interval training, nettle hydroalcoholic consumption and interval training combined with nettle hydroalcoholic consumption were associated with a significant increase in heat shock protein 70 and a significant decrease in extracellular matrix metalloproteinase inducer in C57 mice with melanoma cancer. Therefore, it seems that intermittent exercises and nettle hydroalcoholic consumption can help regulate growth and immune factors in melanoma cancer.
In recent years, due to fewer side effects of herbal medicines, the use of plant-derived compounds as anti-cancer drugs has increased significantly. Clinical studies show that nettle species contain compounds that show activity against cancer cells (16,17). Exercise can also reduce the risk of cancer by changing the response of immune factors (18). Wennerberg et al. (2020) found in a breast cancer model that incorporating 30 minutes of treadmill running five days per week during the anti-PD-1/radiotherapy course reduced tumor-infiltrating myeloid-derived suppressor cells and increased the infiltration of tumor cells. becomes CD8+ T, which is more useful for the function of immune cells (19). However, in Crosby et al.'s (2021) research, there was no statistically significant change in quality of life, fatigue, physical performance, cardiorespiratory fitness, body composition, psychological distress, cognitive performance, or treatment-related side effects compared to physical activity or exercise (20). Previous reports have shown the antitumor activity of nettle in various human malignancies, such as breast, lung, and prostate cancers (17,22). However, despite the therapeutic benefits of nettle plant, the effects of nettle extract on changes in immune and growth factors in melanoma cancer are not clear. Considering the therapeutic benefits of nettle plant as well as the positive effect of exercise in reducing the effect of interval training and consumption of Urtica dioica hydroalcoholic extract on Heat shock protein 70 (HSP70) and Extracellular matrix metalloproteinase inducer (CD147) in C57 rats with melanoma cancer.
Methods: In this experimental study, 20 C57 rats were randomly divided into four groups include control (cancer), Urtica dioica (cancer), and Urtica dioica - interval training (cancer). One week after the induction of melanoma cancer, the experimental group consumed 30 mg/kg/day nettle ethanol extract orally for 8 weeks. The interval exercise program included running on a treadmill 60 minutes at a speed of 28 meters per minute, five days a week for six weeks. The HSP70 and CD147 ranks were measured by Real time PCR. The data were analyzed and analyzed by One -way variance analysis and the Toky's test at the p<0.05.
Results: The results showed that interval training, Urtica dioica hydroalcoholic extract and interval training with Urtica dioica hydroalcoholic extract consumption led to significant increase in the amount of HSP70 and significant decrease in the amount of CD147 in C57 rats with melanoma cancer (P<0.001).
Conclusion: The findings of the present research show that interval training led to a significant increase in the level of heat shock protein 70 and a significant decrease in the level of extracellular matrix metalloproteinase inducer in C57 mice with melanoma cancer. The findings of the present research are consistent with some results of previous studies (19,25). HSP70 induction depends on exercise intensity. High-intensity exercise has a greater effect on stimulating heat shock reactions (26). It seems that one of the effective mechanisms of exercise training on the levels of heat shock proteins is the increase in body temperature and the occurrence of oxidative stress during physical activity, which can be the reason for the increase of these markers after exercise. One of the important mechanisms of CD147 effect in promoting cancer metastasis is the metabolic regulation of the tumor microenvironment through interaction with specific MCTs, such as MCT4, which helps to facilitate lactate transport and tumor glycolysis (29,30). Little is known about the regulation of heat shock proteins in CD147 expression. In one study, it was shown that the reduction of the HSP70 protein family was associated with the increase of CD147 protein expression in human cancer cell tumors, suggesting that the negative regulation of the HSP70 protein family maybe It can increase the migration of cancer cells by upregulating CD147. This hypothesis is supported by findings that the HSP70 protein family negatively regulates the abundance and membrane expression of CD147 protein in cancer cells (9). Also, the results of our study show that nettle hydroalcoholic consumption led to a significant increase in the level of heat shock protein 70 and a significant decrease in the level of extracellular matrix metalloproteinase inducer in C57 mice with melanoma cancer. Stinging nettle extract may exert biological anticancer activities through various mechanisms, including antioxidant and antimutagenic properties, induction or inhibition of key processes in cellular metabolism, and the ability to activate apoptotic pathways (17). The most likely explanation for the significant anticancer effect of nettle is its content of flavonoids and other known molecules and/or as yet unknown substances. In addition, the findings of our study show that interval training with the consumption of nettle hydroalcoholic significantly led to a further decrease in the level of extracellular matrix metalloproteinase inducer in C57 mice with melanoma cancer. Therefore, it is possible that intermittent exercises in combination with nettle hydroalcoholic consumption may lead to a more effective regulation of immune factors in melanoma cancer, but a definitive statement requires more research in this field. The main strength of the present study is to compare the effectiveness of several interventions to identify the best intervention. The current approach results in more informed decisions. There were also limitations in the present research, among which we can point out the small number of samples in the present research, therefore, a similar study with the measurement of these indicators in a high number of samples is suggested. It is also suggested that similar research be done by measuring immune growth factors following other exercise protocols. The results of the present study showed that interval training, nettle hydroalcoholic consumption and interval training combined with nettle hydroalcoholic consumption were associated with a significant increase in heat shock protein 70 and a significant decrease in extracellular matrix metalloproteinase inducer in C57 mice with melanoma cancer. Therefore, it seems that intermittent exercises and nettle hydroalcoholic consumption can help regulate growth and immune factors in melanoma cancer.
Keywords: Melanoma, Intermittent exercise, Urtica dioica hydroalcoholic, Heat shock protein 70, Extracellular matrix metalloproteinase inducer
Type of Study: Research |
Subject:
Exercise Physiology
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