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- Title
Novel ANO1 Inhibitor from Mallotus apelta Extract Exerts Anticancer Activity through Downregulation of ANO1.
- Authors
Seo, Yohan; Anh, Nguyen Hoang; Heo, Yunkyung; Park, So-Hyeon; Kiem, Phan Van; Lee, Yechan; Yen, Duong Thi Hai; Jo, Sungwoo; Jeon, Dongkyu; Tai, Bui Huu; Nam, Nguyen Hoai; Minh, Chau Van; Kim, Seung Hyun; Nhiem, Nguyen Xuan; Namkung, Wan
- 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.
- Subjects
CHLORIDE channels; CYSTIC fibrosis transmembrane conductance regulator; SQUAMOUS cell carcinoma; PROSTATE cancer; CELL migration
- Publication
International Journal of Molecular Sciences, 2020, Vol 21, Issue 18, p6470
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms21186470