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.
Original language | English |
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Pages (from-to) | 1025-1042 |
Number of pages | 18 |
Journal | Journal of Cellular Physiology |
Volume | 236 |
Issue number | 2 |
DOIs | |
Publication status | Published - 2021 Feb |
Keywords
- apoptosis
- calcium homeostasis
- osthole
- ovarian cancer
- zebrafish
ASJC Scopus subject areas
- Physiology
- Clinical Biochemistry
- Cell Biology