The effects of metformin on the hippo pathway in the proliferation of melanoma cancer cells: a preclinical study

Abstract

YAP and TAZ, two closely related transcriptional regulators, have crucial roles in tissue repair upon injury, organ size control, and cancer treatment. Some drugs, such as metformin, that alter cell metabolism can play a role in the regulation of the Hippo pathway. The cells were treated with various concentrations of metformin, dacarbazine (IC₅₀), and both of them. The evaluation of the biomarker and proteins was performed by FACS and immunoblotting, respectively. Cell viability was reduced by 50% after 24 h. Data showed that metformin treatment down-regulated YAP and TAZ (p = .002) expressions and enhanced YAP phosphorylation (p < .001). Metformin, alone and in combination, inhibited the growth and viability of melanoma cells in vitro. The increase in the phosphorylation of YAP renders it a potential target in the development of anticancer drugs. This study showed the effects of metformin on the inhibition of oncogenic YAP and TAZ in the proliferation of melanoma cells.

Keywords:

• Melanoma
• cancer stem cells
• hippo pathway
• YAP/TAZ
• CD133

Acknowledgements

This paper was part of a Ph.D. thesis (research project number: 96GCU3M1293) that was supported by the grant from the School of Veterinary Medicine, Shiraz University, Shiraz, Iran, and Applied Physiology Research Centre, Isfahan University of Medical Sciences, Isfahan, Iran. The department of Haematology, Oncology, and Molecular Medicine of Istituto Superiore di Sanità supported the laboratory activities. We would like to thank all the members of this department, especially Dr Nedaienia and professor Fiori.

Disclosure statement

All authors declare to have no conflicts of interest.