Diethylstilbestrol, a novel ano1 inhibitor, exerts an anticancer effect on non-small cell lung cancer via inhibition of ano1

Yohan Seo, Sung Baek Jeong, Joo Han Woo, Oh Bin Kwon, Sion Lee, Hye In Oh, Sungwoo Jo, Seon Ju Park, Wan Namkung, Uk Yeol Moon, Sungwoo Lee

Research output: Contribution to journalArticlepeer-review

Abstract

Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer-related mortality; thus, therapeutic targets continue to be developed. Anoctamin1 (ANO1), a novel drug target considered for the treatment of NSCLC, is a Ca2+-activated chloride channel (CaCC) overexpressed in various carcinomas. It plays an important role in the development of cancer; however, the role of ANO1 in NSCLC is unclear. In this study, diethylstilbestrol (DES) was identified as a selective ANO1 inhibitor using high-throughput screening. We found that DES inhibited yellow fluorescent protein (YFP) fluorescence reduction caused by ANO1 activation but did not inhibit cystic fibrosis transmembrane conductance regulator channel activity or P2Y activation-related cytosolic Ca2+ levels. Additionally, electrophysiological analyses showed that DES significantly reduced ANO1 channel activity, but it more potently reduced ANO1 protein levels. DES also inhibited the viability and migration of PC9 cells via the reduction in ANO1, phospho-ERK1/2, and phospho-EGFR levels. Moreover, DES induced apoptosis by increasing caspase-3 activity and PARP-1 cleavage in PC9 cells, but it did not affect the viability of hepatocytes. These results suggest that ANO1 is a crucial target in the treatment of NSCLC, and DES may be developed as a potential anti-NSCLC therapeutic agent.

Original languageEnglish
Article number7100
JournalInternational journal of molecular sciences
Volume22
Issue number13
DOIs
Publication statusPublished - 2021 Jul 1

Bibliographical note

Funding Information:
Funding: This research was funded by the National Research Foundation of Korea (grant number NRF-2021R1F1A1060694 and NRF-2019R1F1A1063245). This research was also supported by a grant of the Daegu Gyeongbuk/Osong Medical Cluster R&D Project funded by the Ministry of Science and ICT; the Ministry of Trade, Industry and Energy; and the Ministry of Health and Welfare, Korea (grant number: HI19C0760).

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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