期刊
JOURNAL OF CELLULAR PHYSIOLOGY
卷 236, 期 2, 页码 1025-1042出版社
WILEY
DOI: 10.1002/jcp.29913
关键词
apoptosis; calcium homeostasis; osthole; ovarian cancer; zebrafish
资金
- National Research Foundation of Korea Grant - Ministry of Science and ICT, Republic of Korea [2018R1C1B6009048]
Osthole, a natural coumarin, shows promising anticancer effects against ovarian cancer by targeting the endoplasmic reticulum-mitochondrial axis and phosphatidylinositol 3-kinase/mitogen-activated protein kinase signaling pathway. Its pharmacological potential is demonstrated in a three-dimensional tumor-formation model using the zebrafish xenograft assay, indicating strong potential as a pharmacological agent for targeting ovarian cancer.
Osthole is a natural coumarin found in a variety of plants and has been reported to have diverse biological functions, including antimicrobial, antiviral, immunomodulatory, and anticancer effects. Here, we investigated the natural derivative osthole as a promising anticancer compound against ovarian cancer and evaluated its ability to suppress and abrogate tumor progression. In addition, we found the endoplasmic reticulum-mitochondrial axis-mediated anticancer mechanisms of osthole against ES2 and OV90 ovarian cancer cells and demonstrated its calcium-dependent pharmacological potential. Mechanistically, osthole was found to target the phosphatidylinositol 3-kinase/mitogen-activated protein kinase signaling pathway to facilitate tumor suppression in ovarian cancer. Furthermore, we identified the effects of osthole in a three-dimensional tumor-formation model using the zebrafish xenograft assay, providing convincing evidence of the pharmacological effects of osthole within the anchorage-independent tumor microenvironment. These findings suggest that osthole has strong potential as a pharmacological agent for targeting ovarian cancer.
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