Effects of the exercise-inducible myokine irisin on proliferation and malignant properties of ovarian cancer cells through the HIF-1 α signaling pathway

Abstract

Background: Exercise has been shown to be associated with reduced risk and improving outcomes of several types of cancers. Irisin -a novel exercise-related myokine- has been proposed to exert beneficial effects in metabolic disorders including cancer. No previous studies have investigated whether irisin may regulate malignant characteristics of ovarian cell lines. Methods: In the present study, we aimed to explore the effect of irisin on viability and proliferation of ovarian cancer cells which was examined by MTT assay. Then, we evaluated migratory and invasive ability of the cells via transwell assays. Moreover, the percentage of apoptosis induction was determined by flowcytometery. Furthermore, the mRNA expression level of genes related to the aerobic respiration (HIF-1α, c-Myc, LDHA, PDK1 and VEGF) were detected by real-time PCR. Results: Our data revealed that irisin treatment significantly attenuated the proliferation, migration and invasion of ovarian cancer cells. Besides, irisin induced apoptosis in ovarian cancer cells. We also observed that irisin regulated the expression of genes involved in aerobic respiration of ovarian cancer cells. Conclusion: Our results indicate that irisin may play a crucial role in inhibition of cell growth and malignant characteristics of ovarian cancer. This findings may open up avenues for future studies to identify the further therapeutic use of irisin in ovarian cancer management.

Mechanisms Underlying the Rarity of Skeletal Muscle Cancers

“…Furthermore, in gastric carcinoma cells, irisin treatment or overexpression inhibited migration and invasion, but did not affect proliferation [154]. Moreover, in ovarian cancer cells, irisin antagonized hypoxic cell signaling induced by hypoxia-inducible factor-1α [51], suggesting that irisin may interfere with the tumor response to hypoxia. In two of three ovarian cancer cell lines, it also reduced expression of vascular endothelial growth factor (VEGF), which is essential for intra-tumoral angiogenesis [155].…”

Mechanisms Underlying the Rarity of Skeletal Muscle Cancers

“…Furthermore, in gastric carcinoma cells, irisin treatment or overexpression inhibited migration and invasion but did not affect proliferation [178]. Moreover, in ovarian cancer cells, irisin antagonized hypoxic cell signaling induced by hypoxia-inducible factor-1α [77], suggesting that irisin may interfere with the tumor response to hypoxia. In two of three ovarian cancer cell lines, it also reduced the expression of vascular endothelial growth factor (VEGF), which is essential for intra-tumoral angiogenesis [179].…”

Secretome from Magnetically Stimulated Muscle Exhibits Anticancer Potency: Novel Preconditioning Methodology Highlighting HTRA1 Action

“…The myokine pool consists of a collection of cytokines and other bioactive agents that, following their release into the interstitial fluid and bloodstream, interact with muscle and other tissues to modulate their metabolism and inflammatory status. Certain exercise-induced myokines (exerkines) are known to stymie cancer development and progression by inhibiting malignant proliferation, epithelialmesenchymal (EMT) transition, migration, and invasion [7,15,16,21,22] as well as make the tumor microenvironment less hospitable for cancer progression [21]. Myokines mitigate cancer-permissive comorbidities such as obesity, low-grade inflammation, and dysfunctional immune responses [7,20].…”