Cinobufagin Exerts Anticancer Activity in Oral Squamous Cell Carcinoma Cells through Downregulation of ANO1

Autor: Wan Namkung, Yechan Lee, Dongkyu Jeon, Eunhee Yang, Sungwoo Jo
Jazyk: angličtina
Rok vydání: 2021
Předmět:
QH301-705.5
Cell
Down-Regulation
Antineoplastic Agents
Catalysis
Article
Inorganic Chemistry
ANO1
STAT3
chemistry.chemical_compound
Mice
Downregulation and upregulation
medicine
Tumor Cells
Cultured
Animals
Humans
Physical and Theoretical Chemistry
Biology (General)
Cinobufagin
Molecular Biology
QD1-999
Spectroscopy
Anoctamin-1
Chloride channel activity
Cell Proliferation
biology
Cell growth
Organic Chemistry
Cell migration
General Medicine
Smooth muscle contraction
cinobufagin
CAL-27
Computer Science Applications
Neoplasm Proteins
Bufanolides
Gene Expression Regulation
Neoplastic
Mice
Inbred C57BL
oral squamous cell carcinoma
Chemistry
stomatognathic diseases
medicine.anatomical_structure
chemistry
biology.protein
Cancer research
Carcinoma
Squamous Cell
Mouth Neoplasms
Drug Screening Assays
Antitumor
anoctamin 1
Zdroj: International Journal of Molecular Sciences
Volume 22
Issue 21
International Journal of Molecular Sciences, Vol 22, Iss 12037, p 12037 (2021)
ISSN: 1422-0067
Popis: Anoctamin1 (ANO1), a calcium-activated chloride channel, is frequently overexpressed in several cancers, including oral squamous cell carcinoma (OSCC). OSCC is a highly aggressive cancer and the most common oral malignancy. ANO1 has been proposed as a potential candidate for targeted anticancer therapy. In this study, we performed a cell-based screening to identify novel regulators leading to the downregulation of ANO1, and discovered cinobufagin, which downregulated ANO1 expression in oral squamous cell carcinoma CAL-27 cells. ANO1 protein levels were significantly reduced by cinobufagin in a dose-dependent manner with an IC50 value of ~26 nM. Unlike previous ANO1 inhibitors, short-term (≤10 min) exposure to cinobufagin did not alter ANO1 chloride channel activity and ANO1-dependent intestinal smooth muscle contraction, whereas long-term (24 h) exposure to cinobufagin significantly reduced phosphorylation of STAT3 and mRNA expression of ANO1 in CAL-27 cells. Notably, cinobufagin inhibited cell proliferation of CAL-27 cells expressing high levels of ANO1 more potently than that of ANO1 knockout CAL-27 cells. In addition, cinobufagin significantly reduced cell migration and induced caspase-3 activation and PARP cleavage in CAL-27 cells. These results suggest that downregulation of ANO1 by cinobufagin is a potential mechanism for the anticancer effect of cinobufagin in OSCC.
Databáze: OpenAIRE
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