Antitumor Activity of the Cardiac Glycoside αlDiginoside by Modulating Mcl-1 in Human Oral Squamous Cell Carcinoma Cells
Open Access
- 26 October 2020
- journal article
- research article
- Published by MDPI AG in International Journal of Molecular Sciences
- Vol. 21 (21), 7947
- https://doi.org/10.3390/ijms21217947
Abstract
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, IC50 < 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.This publication has 50 references indexed in Scilit:
- Cardiac glycosides in cancer therapy: from preclinical investigations towards clinical trialsInvestigational New Drugs, 2013
- Inhibition of Jak-STAT3 pathway enhances bufalin-induced apoptosis in colon cancer SW620 cellsWorld Journal of Surgical Oncology, 2012
- Cardiotonic steroids attenuate ERK phosphorylation and generate cell cycle arrest to block human hepatoma cell growthThe Journal of Steroid Biochemistry and Molecular Biology, 2011
- Bufadienolide compounds sensitize human breast cancer cells to TRAIL-induced apoptosis via inhibition of STAT3/Mcl-1 pathwayApoptosis, 2011
- Dysregulated molecular networks in head and neck carcinogenesisOral Oncology, 2009
- Cardiotonic steroids on the road to anti-cancer therapyBiochimica et Biophysica Acta (BBA) - Reviews on Cancer, 2007
- Phase 1 trial of Anvirzel™ in patients with refractory solid tumorsInvestigational New Drugs, 2006
- Role of poly(ADP-ribose) polymerase in rapid intracellular acidification induced by alkylating DNA damageProceedings of the National Academy of Sciences of the United States of America, 2001
- The role of cyclin E in the regulation of entry into S phasePublished by Springer Science and Business Media LLC ,1995
- Cardenolide glycosides of Strophanthus divaricatusPhytochemistry, 1987