Geraniin-mediated apoptosis by cleavage of focal adhesion kinase through up-regulation of Fas ligand expression in human melanoma cells

Molecular Nutrition & Food Research
Jang-Chang LeeTzong-Der Way

Abstract

Geraniin, a form of tannin separated from geranium, causes cell death through induction of apoptosis; however, cell death characteristics for geraniin have not yet been elucidated. Here, we investigated the mechanism of geraniin-induced apoptosis in human melanoma cells and demonstrated that geraniin was able to induce cell apoptosis in a concentration- and time-dependent manner. We also examined the signaling pathway related to geraniin-induced apoptosis. To clarify the relationship between focal adhesion kinase (FAK) and geraniin-induced apoptosis, we treated human melanoma cells with geraniin and found that this resulted dose- and time-dependent degradation in FAK. However, FAK cleavage was significantly inhibited when cells were pretreated with a selective inhibitor of caspase-3 (Ac-Asp-Glu-Val-Asp-CHO). Here, we demonstrated for the first time that geraniin triggered cell death by caspase-3-mediated cleavage of FAK. There were two possible mechanisms for activating caspase-3, mitochondria-mediated and receptor-mediated apoptosis. To confirm the geraniin-relevant signaling pathway, using immunoblot analysis we found that geraniin-induced apoptosis was associated with the up-regulation of Fas ligand expression, the activatio...Continue Reading

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Citations

Sep 26, 2013·PloS One·Antonio VassalloAntonella Leone
Dec 3, 2013·Canadian Journal of Physiology and Pharmacology·Jia LiLinna Pan
Sep 13, 2011·European Journal of Pharmacology·Jang-Chang LeeSheng-Chu Kuo
Apr 2, 2013·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·So Jin BingYoungheun Jee
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Jan 24, 2020·European Journal of Medicinal Chemistry·Thadeu E M M CostaCarmen Penido

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