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Antitumor Activity of the Cardiac Glycoside αlDiginoside by Modulating Mcl-1 in Human Oral Squamous Cell Carcinoma Cells

We recently isolated a cardiac glycoside (CG), αldiginoside, from an indigenous plant in Taiwan, which exhibits potent tumor-suppressive efficacy in oral squamous cell carcinoma (OSCC) cell lines (SCC2095 and SCC4, IC(50) < 0.2 µM; 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT...

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Autores principales: Weng, Jing-Ru, Lin, Wei-Yu, Bai, Li-Yuan, Hu, Jing-Lan, Feng, Chia-Hsien
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7663359/
https://www.ncbi.nlm.nih.gov/pubmed/33114727
http://dx.doi.org/10.3390/ijms21217947
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author Weng, Jing-Ru
Lin, Wei-Yu
Bai, Li-Yuan
Hu, Jing-Lan
Feng, Chia-Hsien
author_facet Weng, Jing-Ru
Lin, Wei-Yu
Bai, Li-Yuan
Hu, Jing-Lan
Feng, Chia-Hsien
author_sort Weng, Jing-Ru
collection PubMed
description We recently isolated a cardiac glycoside (CG), αldiginoside, from an indigenous plant in Taiwan, which exhibits potent tumor-suppressive efficacy in oral squamous cell carcinoma (OSCC) cell lines (SCC2095 and SCC4, IC(50) < 0.2 µM; 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays). Here, we report that αldiginoside 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. αldiginoside induced apoptosis, as indicated by caspase activation and poly (ADP-ribose) polymerase (PARP) cleavage. Equally important, αldiginoside reduced Mcl-1 expression through protein degradation, and overexpression of Mcl-1 partially protected SCC2095 cells from αldiginoside’s cytotoxicity. Taken together, these data suggest the translational potential of αldiginoside to foster new therapeutic strategies for OSCC treatment.
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spelling pubmed-76633592020-11-14 Antitumor Activity of the Cardiac Glycoside αlDiginoside by Modulating Mcl-1 in Human Oral Squamous Cell Carcinoma Cells Weng, Jing-Ru Lin, Wei-Yu Bai, Li-Yuan Hu, Jing-Lan Feng, Chia-Hsien Int J Mol Sci Article We recently isolated a cardiac glycoside (CG), αldiginoside, from an indigenous plant in Taiwan, which exhibits potent tumor-suppressive efficacy in oral squamous cell carcinoma (OSCC) cell lines (SCC2095 and SCC4, IC(50) < 0.2 µM; 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays). Here, we report that αldiginoside 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. αldiginoside induced apoptosis, as indicated by caspase activation and poly (ADP-ribose) polymerase (PARP) cleavage. Equally important, αldiginoside reduced Mcl-1 expression through protein degradation, and overexpression of Mcl-1 partially protected SCC2095 cells from αldiginoside’s cytotoxicity. Taken together, these data suggest the translational potential of αldiginoside to foster new therapeutic strategies for OSCC treatment. MDPI 2020-10-26 /pmc/articles/PMC7663359/ /pubmed/33114727 http://dx.doi.org/10.3390/ijms21217947 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Weng, Jing-Ru
Lin, Wei-Yu
Bai, Li-Yuan
Hu, Jing-Lan
Feng, Chia-Hsien
Antitumor Activity of the Cardiac Glycoside αlDiginoside by Modulating Mcl-1 in Human Oral Squamous Cell Carcinoma Cells
title Antitumor Activity of the Cardiac Glycoside αlDiginoside by Modulating Mcl-1 in Human Oral Squamous Cell Carcinoma Cells
title_full Antitumor Activity of the Cardiac Glycoside αlDiginoside by Modulating Mcl-1 in Human Oral Squamous Cell Carcinoma Cells
title_fullStr Antitumor Activity of the Cardiac Glycoside αlDiginoside by Modulating Mcl-1 in Human Oral Squamous Cell Carcinoma Cells
title_full_unstemmed Antitumor Activity of the Cardiac Glycoside αlDiginoside by Modulating Mcl-1 in Human Oral Squamous Cell Carcinoma Cells
title_short Antitumor Activity of the Cardiac Glycoside αlDiginoside by Modulating Mcl-1 in Human Oral Squamous Cell Carcinoma Cells
title_sort antitumor activity of the cardiac glycoside αldiginoside by modulating mcl-1 in human oral squamous cell carcinoma cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7663359/
https://www.ncbi.nlm.nih.gov/pubmed/33114727
http://dx.doi.org/10.3390/ijms21217947
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