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Article

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

1
College of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983, Korea
2
Interdisciplinary Program of Integrated OMICS for Biomedical Science Graduate School, Yonsei University, Seoul 03722, Korea
3
New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu 41061, Korea
4
Graduate University of Sciences and Technology, VAST, 18 Hoang Quoc Viet, Cau Giay, Hanoi 100000, Vietnam
5
Graduate Program of Industrial Pharmaceutical Science, Yonsei University, Incheon 21983, Korea
6
Institute of Marine Biochemistry, Vietnam Academy of Science and Technology (VAST), 18 Hoang Quoc Viet, Cau Giay, Hanoi 100000, Vietnam
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2020, 21(18), 6470; https://doi.org/10.3390/ijms21186470
Received: 20 July 2020 / Revised: 27 August 2020 / Accepted: 2 September 2020 / Published: 4 September 2020
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 (36) 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. View Full-Text
Keywords: Mallotus apelta; anoctamin 1; inhibitor; cytotoxicity; apoptosis Mallotus apelta; anoctamin 1; inhibitor; cytotoxicity; apoptosis
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MDPI and ACS Style

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. Novel ANO1 Inhibitor from Mallotus apelta Extract Exerts Anticancer Activity through Downregulation of ANO1. Int. J. Mol. Sci. 2020, 21, 6470. https://doi.org/10.3390/ijms21186470

AMA Style

Seo Y, Anh NH, Heo Y, Park S-H, Kiem PV, Lee Y, Yen DTH, Jo S, Jeon D, Tai BH, Nam NH, Minh CV, Kim SH, Nhiem NX, Namkung W. Novel ANO1 Inhibitor from Mallotus apelta Extract Exerts Anticancer Activity through Downregulation of ANO1. International Journal of Molecular Sciences. 2020; 21(18):6470. https://doi.org/10.3390/ijms21186470

Chicago/Turabian Style

Seo, Yohan, Nguyen H. Anh, Yunkyung Heo, So-Hyeon Park, Phan V. Kiem, Yechan Lee, Duong T.H. Yen, Sungwoo Jo, Dongkyu Jeon, Bui H. Tai, Nguyen H. Nam, Chau V. Minh, Seung H. Kim, Nguyen X. Nhiem, and Wan Namkung. 2020. "Novel ANO1 Inhibitor from Mallotus apelta Extract Exerts Anticancer Activity through Downregulation of ANO1" International Journal of Molecular Sciences 21, no. 18: 6470. https://doi.org/10.3390/ijms21186470

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