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.
|Number of pages||15|
|Journal||International journal of molecular sciences|
|Publication status||Published - 2020 Sept 2|
Bibliographical noteFunding Information:
Funding: This research was funded by the Vietnam Academy of Science and Technology (DL0000.01/19-20), National Research Foundation of Korea (NRF-2015R1D1A1A01057695, NRF2018R1A6A1A03023718, and NRF-2019R1I1A1A01061117). This research was also supported (in part) by Yonsei University Research Fund 2019 (Project No. 2019-12-0013).
This research was funded by the Vietnam Academy of Science and Technology (DL0000.01/19-20), National Research Foundation of Korea (NRF-2015R1D1A1A01057695, NRF2018R1A6A1A03023718, and NRF-2019R1I1A1A01061117). This research was also supported (in part) by Yonsei University Research Fund 2019 (Project No. 2019-12-0013). The authors would like to thank Hyejin Jeon (College of Pharmacy, Yonsei University), Pham Hai Yen (Institute of Marine Biochemistry, Vietnam Academy of Science and Technology), and Pham The Chinh (Faculty of Chemistry, Thai Nguyen University of Science) for their support to this study.
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Computer Science Applications
- Physical and Theoretical Chemistry
- Organic Chemistry
- Inorganic Chemistry