Antitumor Activity of the Cardiac Glycoside α-L-Diginoside by Modulating Mcl-1 in Human Oral Squamous Cell Carcinoma Cells
We recently isolated a cardiac glycoside (CG), α-L-diginoside, from an indigenous plant in Taiwan, which exhibits potent tumor-suppressive efficacy in oral squamous cell carcinoma (OSCC) cell lines (SCC2095 and SCC4, IC<sub>50</sub> < 0.2 µM; 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenylt...
Main Authors: | , , , , |
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Format: | Article |
Language: | English |
Published: |
MDPI AG
2020-10-01
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Series: | International Journal of Molecular Sciences |
Subjects: | |
Online Access: | https://www.mdpi.com/1422-0067/21/21/7947 |
Summary: | We recently isolated a cardiac glycoside (CG), α-L-diginoside, from an indigenous plant in Taiwan, which exhibits potent tumor-suppressive efficacy in oral squamous cell carcinoma (OSCC) cell lines (SCC2095 and SCC4, IC<sub>50</sub> < 0.2 µM; 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays). Here, we report that α-L-diginoside caused Sphase arrest and apoptosis, through the inhibition of a series of signaling pathways, including those mediated by cyclin E, phospho-CDC25C (p-CDC25C), and janus kinase/signal transducer and activator of transcription (JAK/STAT)3. α-L-diginoside induced apoptosis, as indicated by caspase activation and poly (ADP-ribose) polymerase (PARP) cleavage. Equally important, α-L-diginoside reduced Mcl-1 expression through protein degradation, and overexpression of Mcl-1 partially protected SCC2095 cells from α-L-diginoside’s cytotoxicity. Taken together, these data suggest the translational potential of α-L-diginoside to foster new therapeutic strategies for OSCC treatment. |
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ISSN: | 1661-6596 1422-0067 |