ANO1-downregulation induced by schisandrathera D: a novel therapeutic target for the treatment of prostate and oral cancers

• Published in: Frontiers in pharmacology Vol. 14; p. 1163970
• Main Authors: Park, SeonJu, Das, Raju, Nhiem, Nguyen Xuan, Jeong, Sung Baek, Kim, Minuk, Kim, Dongguk, Oh, Hye In, Cho, Su-Hyeon, Kwon, Oh-Bin, Choi, Jae-Hyeog, Park, Chul Soon, Kim, Song-Rae, Moon, Uk Yeol, Cha, Boksik, Choi, Dong Kyu, Lee, Sungwoo, Namkung, Wan, Woo, Joohan, Seo, Yohan
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 18.05.2023
• Subjects: anoctamin 1; apoptosis; oral cancer; Pharmacology; prostate cancer; protein reduction; Schisandra sphenanthera; apoptosis; prostate cancer; Schisandra sphenanthera; anoctamin 1; oral cancer; protein reduction
• ISSN: 1663-9812; 1663-9812
• DOI: 10.3389/fphar.2023.1163970

Anoctamin 1 (ANO1), a drug target for various cancers, including prostate and oral cancers, is an intracellular calcium-activated chloride ion channel that plays various physiopathological roles, especially in the induction of cancer growth and metastasis. In this study, we tested a novel compound isolated from , known as schisandrathera D, for its inhibitory effect on ANO1. Schisandrathera D dose-dependently suppressed the ANO1 activation-mediated decrease in fluorescence of yellow fluorescent protein; however, it did not affect the adenosine triphosphate-induced increase in the intracellular calcium concentration or forskolin-induced cystic fibrosis transmembrane conductance regulator activity. Specifically, schisandrathera D gradually decreased the levels of ANO1 protein and significantly reduced the cell viability in ANO1-expressing cells when compared to those in ANO1-knockout cells. These effects could be attributed to the fact that schisandrathera D displayed better binding capacity to ANO1 protein than the previously known ANO1 inhibitor, Ani9. Finally, schisandrathera D increased the levels of caspase-3 and cleaved poly (ADP-ribose) polymerase 1, thereby indicating that its anticancer effect is mediated through apoptosis. Thus, this study highlights that schisandrathera D, which reduces ANO1 protein levels, has apoptosis-mediated anticancer effects in prostate and oral cancers, and thus, can be further developed into an anticancer agent.