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羟基酪醇诱导人黑色素瘤细胞凋亡死亡。

The Hydroxytyrosol Induces the Death for Apoptosis of Human Melanoma Cells.

机构信息

Istituto per la Ricerca e l'Innovazione Biomedica (IRIB), Consiglio Nazionale delle Ricerche (CNR), Via Ugo La Malfa 153, 90146 Palermo, Italy.

出版信息

Int J Mol Sci. 2020 Oct 29;21(21):8074. doi: 10.3390/ijms21218074.

Abstract

Melanoma is the most aggressive form of skin cancer and one of the most treatment-refractory malignancies. In metastatic melanoma cell lines, we analysed the anti-proliferative and pro-apoptotic potentials of a phenolic component of olive oil, the hydroxytyrosol. In particular, through MTS assay, DeadEnd™ 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 γH2AX 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. 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.

摘要

黑色素瘤是最具侵袭性的皮肤癌之一,也是最难治疗的恶性肿瘤之一。在转移性黑色素瘤细胞系中,我们分析了橄榄油的一种酚类成分——羟基酪醇的抗增殖和促凋亡潜力。具体来说,通过 MTS 检测、DeadEnd™比色 TUNEL 检测、Annexin V 结合和 PI 摄取、Western blot 实验、细胞内活性氧(ROS)分析和细胞集落实验,我们表明羟基酪醇处理可显著降低细胞活力,诱导黑色素瘤细胞凋亡死亡。此外,我们还表明,羟基酪醇处理黑色素瘤细胞可显著增加 p53 和 γH2AX 的表达,显著降低 AKT 的表达,并抑制细胞集落形成能力。最后,我们提出,细胞内活性氧(ROS)的增加可能与凋亡激活和黑色素瘤生长抑制途径的调节有关,这可能是羟基酪醇在黑色素瘤中发挥作用的策略。因此,由于羟基酪醇在抑制黑色素瘤生长方面的作用,其治疗可能会深度干扰黑色素瘤的进展,为治疗这种高度侵袭性肿瘤提供一种有前景的治疗选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfee/7662312/34fb3a5b73c2/ijms-21-08074-g001.jpg

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