Melanoma is one of the most aggressive cancers worldwide and the deadliest form of skin cancer whose incidence rate, unfortunately, is increasing rapidly in western populations. Indeed, metastatic melanoma is one of the most drug-resistant cancer that often acquires the capacity to evade the cytotoxic action of therapeutic options inducing the breakdown of cell death control. Therefore, in the aim to identify new potential therapeutic drugs suitable to overcome the intrinsic survival features acquired by melanoma cells, we studied the role of hydroxytyrosol [2-(3,4-dihydroxyphenyl) ethanol or 3-hydroxytyrosol], the major phenolic component of olive oil (1), on the inhibition of human melanoma cell growth and survival. Interestingly, olives and olive oil are crucial components of the Mediterranean diet and their regular intake has been related to reduced risk of several chronic diseases such as cancer (2). Therefore, we improved and increased this field of research analysing in metastatic melanoma cell lines, the anti-proliferative and pro-apoptotic potentials of the hydroxytyrosol (3). In particular, through MTS assay, DeadEnd(TM) Colorimetric TUNEL assay, Annexin V binding and PI uptake, western blot experiment, intracellular reactive oxygen species (ROS) analysis and the cell colony assay, we showed that the hydroxytyrosol treatment remarkably reduces the cell viability inducing the death for apoptosis of melanoma cells. Moreover, we showed that the hydroxytyrosol treatment of melanoma cells leads to a significant increase of p53 and ?H2AX expression, a significant decrease of AKT expression and the inhibition of cell colony formation ability. Finally, we propose that the increased amount of intracellular reactive oxygen species (ROS) that may be related to the regulation of the pathways involved in the activation of apoptosis and in the inhibition of melanoma growth, could be the strategy used by hydroxytyrosol to exert its functions in melanoma. Indeed, hydroxytyrosol is widely accepted in cancer treatment for its anti-tumour properties and low toxicity, therefore, for its role in melanoma growth inhibition, the hydroxytyrosol treatment could deeply interfere with melanoma progression as a promising therapeutic option for the treatment of this highly invasive tumour.
The hydroxytyrosol induces the apoptotic cell death of human melanoma cells.
Francesca Costantini;Caterina Di Sano;Giovanna Barbieri
2023
Abstract
Melanoma is one of the most aggressive cancers worldwide and the deadliest form of skin cancer whose incidence rate, unfortunately, is increasing rapidly in western populations. Indeed, metastatic melanoma is one of the most drug-resistant cancer that often acquires the capacity to evade the cytotoxic action of therapeutic options inducing the breakdown of cell death control. Therefore, in the aim to identify new potential therapeutic drugs suitable to overcome the intrinsic survival features acquired by melanoma cells, we studied the role of hydroxytyrosol [2-(3,4-dihydroxyphenyl) ethanol or 3-hydroxytyrosol], the major phenolic component of olive oil (1), on the inhibition of human melanoma cell growth and survival. Interestingly, olives and olive oil are crucial components of the Mediterranean diet and their regular intake has been related to reduced risk of several chronic diseases such as cancer (2). Therefore, we improved and increased this field of research analysing in metastatic melanoma cell lines, the anti-proliferative and pro-apoptotic potentials of the hydroxytyrosol (3). In particular, through MTS assay, DeadEnd(TM) Colorimetric TUNEL assay, Annexin V binding and PI uptake, western blot experiment, intracellular reactive oxygen species (ROS) analysis and the cell colony assay, we showed that the hydroxytyrosol treatment remarkably reduces the cell viability inducing the death for apoptosis of melanoma cells. Moreover, we showed that the hydroxytyrosol treatment of melanoma cells leads to a significant increase of p53 and ?H2AX expression, a significant decrease of AKT expression and the inhibition of cell colony formation ability. Finally, we propose that the increased amount of intracellular reactive oxygen species (ROS) that may be related to the regulation of the pathways involved in the activation of apoptosis and in the inhibition of melanoma growth, could be the strategy used by hydroxytyrosol to exert its functions in melanoma. Indeed, hydroxytyrosol is widely accepted in cancer treatment for its anti-tumour properties and low toxicity, therefore, for its role in melanoma growth inhibition, the hydroxytyrosol treatment could deeply interfere with melanoma progression as a promising therapeutic option for the treatment of this highly invasive tumour.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
