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

Hyocheol Bae, Jin Young Lee, Jisoo Song, Gwonhwa Song, Whasun Lim

Research output: Contribution to journalArticle

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 languageEnglish
JournalJournal of Cellular Physiology
DOIs
Publication statusAccepted/In press - 2020

Keywords

  • apoptosis
  • calcium homeostasis
  • osthole
  • ovarian cancer
  • zebrafish

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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