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

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 activation of caspase-8, the cleavage of Bid, and the induction of cytochrome c release from mitochondria to the cytosol. Treatment with geraniin caused induction of caspase-3 activity in a dose- and time-dependent manner followed by proteolytic cleavage of poly-(ADP-ribose) polymerase, and DNA fragmentation factor 45. The geraniin-induced apoptosis may provide a pivotal mechanism for its cancer-chemopreventive action.

Geraniin induces apoptotic cell death in human lung adenocarcinoma A549 cells in vitro and in vivo

“…Geraniin has been reported to possess several biological effects, including antioxidant, antitumor, antiviral, and antibacterial activities (Gohar et al 2003;Kang et al 2011;Lee et al 2008;Li et al 2008;Lin et al 2008;Londhe et al 2008;Yang et al 2007). However, to our knowledge, the apoptotic effect of geraniin has not been evaluated in lung cancer cells.…”

Identification of the Plant Compound Geraniin as a Novel Hsp90 Inhibitor

“…Geraniin is a typical ellagitannin because it is composed entirely of common acyl units, such as galloyl, hexahydroxydiphenoyl (HHDP), and dehydrohexahydroxydiphenoyl (DHHDP) groups. Although variousstudies of geraniin have proved its antioxidant, antitumor, and antivirus properties [20], [21], its mechanism of action is still poorly characterized. Herein, we report the results of a panel of chemical and biological approaches that demonstrate that geraniin binds to Hsp90α and inhibits its ATPase activity, thus compromising the stability of some oncogenic client proteins.…”

Antimutagencity of Phyllamentus Embelica

“…In addition, it has the ability to exert inhibitory effects on the critical steps in metastasis, including cell invasion, migration, and invasion. A number of phenolic compounds isolated from the fruit extract are responsible for the antiproliferative component of P. emblica [30]. Its antimetastatic potential could partially be attributed to its capability to induce apoptosis which is associated with the activation of caspases-3 and -7 as well as DNA fragmentation.…”