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| Subject/animal/culture | Tumor/cell model | Treatment/groups | Main results | Authors’ main conclusions | Reference |
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| Lung cancer cells | A549 and NCI-H446 lung cancer cells | Treated with 0, 10, 20, or 50 nM irisin, respectively, for different time periods (0, 24, and 48 h) | (i) Over a range of concentrations (20–50 nM), significantly irisin inhibits A549 cells proliferation as detected by MTT assay
(ii) Irisin may alter the expression of EMT markers in a concentration-dependent manner and indicate that the inhibitory effect of irisin on lung cancer cells invasion and migration may be associated with EMT. | (i) Inhibition of proliferation, migration, and invasion of osteosarcoma cells
(ii) Suppression of IL-6-induced EMT in osteosarcoma cells
(ii) targeting the STAT3/Snail signaling pathway | Shao et al. [8] |
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| Female patients with invasive ductal breast cancer and healthy women | — | Two groups: 101 females with invasive ductal breast cancer and 51 healthy females | (i) Irisin discriminates between patients and healthy individuals at an optimal value of 3.21 μg/ml
(ii) Irisin levels were positively associated with tumor stage
(iii) No significant association between irisin and tumor grade, and irisin and CEA, and CA15-3 and Her2/neu | (i) Irisin may serve as a novel biomarker for breast cancer diagnosis
(ii) An understanding of irisin’s role in health, and disease is lacking | Provatopoulou et al. [9] |
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| Breast cancer cells | MDA-MB-231 cells and MCF-10a cells | MDA-MB-231 and MCF-10a cells were treated with human recombinant nonmodified irisin (INM) or human recombinant modified and active (glycosylated) irisin (IM) | (i) INM did not affect nonmalignant MCF-10a cell viability, but IM decreased it
(ii) Malignant MDA-MB-231 cell viability was significantly reduced by INM, but not IM
(iii) INM decreased cell number while IM did not
(iv) Caspase-3/7 activity was significantly elevated when cells were treated with INM but not when treated with IM
(v) IM enhanced Dox killing at 1.0 μM, while INM enhanced it at all tested concentrations | (i) Irisin is a potential therapeutic agent for cancer
(ii) Irisin may have an anti-inflammatory effect, counteracting the effects of TNF-α
(iii) Irisin affects malignant cells without affecting nonmalignant cells | Gannon et al. [10] |
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| Patients with renal cell cancer and healthy subjects | — | Two groups: 23 patients with renal tumor and 25 healthy individuals | (i) Significantly elevated FNDC5/irisin levels and CEA in patients with renal tumor
(ii) FNDC5 levels showed higher sensitivity and specificity indexes when compared to CEA | (i) Irisin may be a useful marker in the diagnosis of cancer | Altay et al. [11] |
| Patients undergoing liver transplantation and deceased donors | — | Two groups: 18 patients with HCV-related HCC undergoing liver transplantation and 18 deceased liver donors | (i) Irisin mRNA expression was significantly higher in the liver of HCC patients than in liver donors
(ii) SCD-1, NOTCH1, IL-6, and TNF-α were significantly higher in HCC patients than in donors
(iii) Irisin mRNA correlated with the plasma lipid profile (triglycerides), DNL index, and PUFA/SFA ratios | (i) Irisin levels increase in hepatocellular carcinoma as a compensatory mechanism to limit cancer-induced lipogenesis.
(ii) No correlation between hepatic irisin levels and plasma irisin levels, possibly due to plasma irisin levels depending on the sum total of the adipose tissue and skeletal muscle | Gaggini et al. [12] |
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| Prostate cancer cells | DU-145 and PC3 | Treated with 0.1, 1, 10, and 100 nM irisin | (i) Irisin reduced proliferation and cell viability of the DU-145 and PC3 cells when treated with 10 and 100 nM of irisin, respectively | Irisin has a cytotoxic effect on prostate cancer cells on both ± androgen receptors in a dose-dependent manner | Tekin et al. [13] |
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| Patients with colon and rectal cancer | — | 76 CRC patients and 40 healthy controls | (i) Patients with CRC have significantly reduced levels of irisin
(ii) High serum irisin levels had a 78% reduced risk of developing CRC. | (i) Irisin could act as a potential serum diagnostic biomarker for CRC
(ii) Irisin could be a protective factor in CRC development | Zhu et al. [14] |
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| Endometrial, colon, thyroid, and esophageal cell lines | KLE and RL95-2, HT29 and MCA38, SW579 and BHP7, and OE13 and OE33 | Cells were treated with irisin for a period between 24 and 36 hours | (i) No change in cell adhesion or colony number
(ii) No effect on cell proliferation | (i) Irisin did not have an effect of cell proliferation or malignant potential of human and mouse obesity-related cancer cell lines | Moon and Mantzoros [15] |
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| 20 patients with hepatocellular carcinoma and hepatocellular carcinoma cells. | HepG2 and SMCC7721 | Cells were treated with glycosylated and nonmodified irisin for 24 h. | (i) HepG2 and SMCC7721 viability and proliferation increased
(ii) Doxorubicin cytotoxicity was reduced | (i) Irisin regulates liver cancer cell proliferation
(ii) Irisin significantly increases the activation of the PI3K/AKT pathway
(iii) Irisin reduces doxorubicin sensitivity | Shi et al. [16] |
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| 60 BALB/c mice | — | 12 mice as controls and 48 mice receiving carcinogenic MNU | (i) No FNDC5/irisin expression was detected in cancerous stomach tissue
(ii) Significant increase in FNDC5/irisin expression in subcutaneous adipose tissue after development of cancer | (i) Gastric tumors stimulated the release of FNDC5 leading to weight loss | Altay et al. [17] |
| Osteosarcoma cells | U2OS and MG-63 osteosarcoma cells | Osteosarcoma cells were treated with different doses of irisin (0, 25, 50, 100, and 200 ng/ml) for different times (12, 24, and 48 h) and were also treated with and without IL-6 | (i) Irisin significantly suppressed osteosarcoma cell viability after 24 h
(ii) Irisin significantly inhibited osteosarcoma cell proliferation after 48 h
(iii) Irisin reversed the effect of IL-6 and suppressed EMT transition
(iv) Irisin downregulated STAT3 phosphorylation
(v) Irisin inhibits Snail expression via STAT3 pathway | (i) Irisin suppressed metastasis by the inhibition of EMT via the STAT3/Snail pathway
(ii) Irisin suppressed the migration and invasion of osteosarcoma cells
(iii) Irisin reversed the EMT induced by IL-6 | Kong et.al. [18] |
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| 148 female patients with breast cancer | — | — | (i) Patients with spinal metastasis had significantly lower levels of serum irisin
(ii) High serum irisin levels reduced the risk of spinal metastasis by 20% | (i) Irisin has protective qualities against the development of spinal metastasis
(ii) Irisin can be used as a predictive marker for bone metastasis | Zhang et al. [19] |
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| Pancreatic cancer cell lines | MIA PaCa-2 and Panc03.27 | Cells were treated with different concentrations (0, 10, and 100 nM) of E-irisin and P-irisin for 2 weeks | (i) Reduced PaCa-2 and Panc03.27 viability
(ii) Reduction in mobility and invasiveness
(iii) Upgregulation of E-cadherin expression
(iv) Increase in phosphorylation of AMPK | (i) Irisin suppressed invasion and migration of pancreatic cancer cells by inhibiting EMT | Liu et al. [20] |
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