Osthole interacts with an ER‐mitochondria axis and facilitates tumor suppression in ovarian cancer

Abstract 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.