Novel ANO1 Inhibitor from Mallotus apelta Extract Exerts Anticancer Activity through Downregulation of ANO1

Yohan Seo, Nguyen Hoang Anh, Yunkyung Heo, So Hyeon Park, Phan Van Kiem, Yechan Lee, Duong Thi Hai Yen, Sungwoo Jo, Dongkyu Jeon, Bui Huu Tai, Nguyen Hoai Nam, Chau Van Minh, Seung Hyun Kim, Nguyen Xuan Nhiem, Wan Namkung

Research output: Contribution to journalArticle

Abstract

Anoctamin1 (ANO1), a calcium-activated chloride channel, is frequently overexpressed in several cancers, including human prostate cancer and oral squamous cell carcinomas. ANO1 plays a critical role in tumor growth and maintenance of these cancers. In this study, we have isolated two new compounds (1 and 2) and four known compounds (3-6) from Mallotus apelta. These compounds were evaluated for their inhibitory effects on ANO1 channel activity and their cytotoxic effects on PC-3 prostate cancer cells. Interestingly, compounds 1 and 2 significantly reduced both ANO1 channel activity and cell viability. Electrophysiological study revealed that compound 2 (Ani-D2) is a potent and selective ANO1 inhibitor, with an IC50 value of 2.64 μM. Ani-D2 had minimal effect on cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel activity and intracellular calcium signaling. Notably, Ani-D2 significantly reduced ANO1 protein expression levels and cell viability in an ANO1-dependent manner in PC-3 and oral squamous cell carcinoma CAL-27 cells. In addition, Ani-D2 strongly reduced cell migration and induced activation of caspase-3 and cleavage of PARP in PC-3 and CAL-27 cells. This study revealed that a novel ANO1 inhibitor, Ani-D2, has therapeutic potential for the treatment of several cancers that overexpress ANO1, such as prostate cancer and oral squamous cell carcinoma.

Original languageEnglish
JournalInternational journal of molecular sciences
Volume21
Issue number18
DOIs
Publication statusPublished - 2020 Sep 4

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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    Seo, Y., Anh, N. H., Heo, Y., Park, S. H., Kiem, P. V., Lee, Y., Yen, D. T. H., Jo, S., Jeon, D., Tai, B. H., Nam, N. H., Minh, C. V., Kim, S. H., Nhiem, N. X., & Namkung, W. (2020). Novel ANO1 Inhibitor from Mallotus apelta Extract Exerts Anticancer Activity through Downregulation of ANO1. International journal of molecular sciences, 21(18). https://doi.org/10.3390/ijms21186470