Therapeutic approach to target mesothelioma cancer cells using the Wnt antagonist, secreted frizzled-related protein 4: Metabolic state of cancer cells
MetadataShow full item record
Malignant mesothelioma (MM) is an aggressive cancer, characterized by rapid progression, along with late metastasis and poor patient prognosis. It is resistant to many forms of standard anti-cancer treatment. In this study, we determined the effect of secreted frizzled-related protein 4 (sFRP4), a Wnt pathway inhibitor, on cancer cell proliferation and metabolism using the JU77 mesothelioma cell line.Treatment with sFRP4 (250. pg/ml) resulted in a significant reduction of cell proliferation. The addition of the Wnt activator Wnt3a (250. pg/ml) or sFRP4 had no significant effect on ATP production and glucose utilisation in JU77 cells at both the 24 and 48. h time points examined. We also examined their effect on Akt and Glycogen synthase kinase-3 beta (GSK3ß) phosphorylation, which are both important components of Wnt signalling and glucose metabolism. We found that protein phosphorylation of Akt and GSK3ß varied over the 24. h and 48. h time points, with constitutive phosphorylation of Akt at serine 473 (pAkt) decreasing to its most significant level when treated with Wnt3a+sFRP4 at the 24. h time point. A significant reduction in the level of Cytochrome c oxidase was observed at the 48. h time point, when sFRP4 and Wnt3a were added in combination.We conclude that sFRP4 may function, in part, to reduce/alter cancer cell metabolism, which may lead to sensitisation of cancer cells to chemotherapeutics, or even cell death.
Showing items related by title, author, creator and subject.
Wnt antagonist, secreted frizzled-related protein 4 (sFRP4), increases chemotherapeutic response of glioma stem-like cellsWarrier, S.; Balu, S.; Kumar, Alan Prem; Michael, M.; Dharmarajan, Arunasalam (2014)Malignant gliomas have a highly tumorigenic subpopulation, termed cancer stem cells (CSCs), that drives tumor formation and proliferation. CSCs possess inherent resistance mechanisms against radiation- and chemotherapy- ...
Secreted frizzled-related protein 4 inhibits glioma stem-like cells by reversing epithelial to mesenchymal transition, inducing apoptosis and decreasing cancer stem cell propertiesBhuvanalakshmi, G.; Arfuso, Frank; Millward, M.; Dharmarajan, Arunasalam; Warrier, Sudha (2015)The Wnt pathway is integrally involved in regulating self-renewal, proliferation, and maintenance of cancer stem cells (CSCs). We explored the effect of the Wnt antagonist, secreted frizzled-related protein 4 (sFRP4), in ...
Breast cancer stem-like cells are inhibited by diosgenin, a steroidal saponin, by the attenuation of the Wnt ß-catenin signaling via the Wnt antagonist secreted frizzled related protein-4Bhuvanalakshmi, G.; Basappa; Rangappa, K.; Dharmarajan, Arunasalam; Sethi, G.; Kumar, Alan Prem; Warrier, Sudha (2017)© 2017 Bhuvanalakshmi, Basappa, Rangappa, Dharmarajan, Sethi, Kumar and Warrier.Background: Identification of breast cancer stem cells as the chemo-resistant and tumor-initiating population represents an important milestone ...