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ANO1-downregulation induced by schisandrathera D: a novel therapeutic target for the treatment of prostate and oral cancers
- Source :
- Frontiers in Pharmacology, Vol 14 (2023)
- Publication Year :
- 2023
- Publisher :
- Frontiers Media S.A., 2023.
-
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.
Details
- Language :
- English
- ISSN :
- 16639812
- Volume :
- 14
- Database :
- Directory of Open Access Journals
- Journal :
- Frontiers in Pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.253af63eabeb4b5a869570c1e0770388
- Document Type :
- article
- Full Text :
- https://doi.org/10.3389/fphar.2023.1163970