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

Seon Ju Park, Raju Das, Nguyen Xuan Nhiem, Sung Baek Jeong, Minuk Kim, Dongguk Kim, Hye In Oh, Su Hyeon Cho, Oh Bin Kwon, Jae Hyeog Choi, Chul Soon Park, Song Rae Kim, Uk Yeol Moon, Boksik Cha, Dong Kyu Choi, Sungwoo Lee, Wan Namkung, Joohan Woo, Yohan Seo

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

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 Schisandra sphenanthera, 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.

Original languageEnglish
Article number1163970
JournalFrontiers in Pharmacology
Volume14
DOIs
StatePublished - 2023

Keywords

  • anoctamin 1
  • apoptosis
  • oral cancer
  • prostate cancer
  • protein reduction
  • Schisandra sphenanthera

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