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

Abstract

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 cancer cell lines. 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 the migratory and invasive abilities of the cells via transwell assays. Moreover, the percentage of apoptosis induction was determined by flow cytometry. Furthermore, the mRNA expression level of genes related to the aerobic respiration (HIF-1α, c-Myc, LDHA, PDK1 and VEGF) was detected by real-time PCR. Our data revealed that irisin treatment significantly attenuated the proliferation, migration and invasion of ovarian cancer cells. Additionally, 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. Our results indicated that irisin may play a crucial role in inhibition of cell growth and malignant characteristics of ovarian cancer. These findings may open up avenues for future studies to identify the further therapeutic use of irisin in ovarian cancer management.

Effects of Irisin on the Reproductive System of Obese Female Rats Induced by a High-Fat Diet

“…This effect of obesity on apoptosis of ovarian follicles shown in this study is supported by recent studies demonstrating that diet-induced obesity is known to increase apoptotic ovarian follicles in rodents (13,24,42). Irisin has also been demonstrated to increase apoptosis in ovarian cancer cells and breast cancer cells (43,44). Similarly, to our knowledge, our findings have shown for the first time that irisin induces apoptosis in the ovarian tissue of lean rats.…”

Effects of Exercise-Induced Changes in Myokine Expression on the Tumor Microenvironment

“…Irisin treatment of OC cells decreased hypoxia-inducible factor-1-alpha (HIF-1α) and VEGF expression, possibly favoring tumorigenesis. Aside from these observations, an induction of apoptosis was also observed [103]. In another in vitro study on pancreatic cancer, ferroptosis, an iron-dependent type of apoptosis in which reactive oxygen species accumulate, was enhanced when cells were treated with irisin.…”

“…In regard to aerobic metabolism genes, irisin had an inhibitory effect on VEGF expression, while the expression of other observed genes varied among cell lines. The effects on metalloproteases are still inconclusive and will need further studies, which involve the effect of different exercise interventions on myokines and cancer cells [103].…”

The role of myokines in cancer: crosstalk between skeletal muscle and tumor

“…Exposure to irisin or overexpression of FNDC5/irisin diminished migration and invasion in different types of human cancer cell lines ( 43 , 45 ). In ovarian cancer cell lines, irisin blocked hypoxia-inducible factor 1α signaling pathways responsible for the expression of metastasis markers, supporting its anti-metastatic activities ( 46 ). In the xenograft glioblastoma mouse model, administration of irisin dramatically repressed tumor growth ( 47 ).…”