Osthole interacts with an ER-mitochondria axis and facilitates tumor suppression in ovarian cancer.,Journal of Cellular Physiology

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Osthole interacts with an ER-mitochondria axis and facilitates tumor suppression in ovarian cancer.
Journal of Cellular Physiology ( IF 4.5 ) Pub Date : 2020-07-22 , DOI: 10.1002/jcp.29913
Hyocheol Bae ₁ , Jin-Young Lee ₂ , Jisoo Song ₃ , Gwonhwa Song ₁ , Whasun Lim ₃

Affiliation

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.

中文翻译：

Osthole 与 ER-线粒体轴相互作用并促进卵巢癌中的肿瘤抑制。

Osthole 是一种存在于多种植物中的天然香豆素，据报道具有多种生物学功能，包括抗菌、抗病毒、免疫调节和抗癌作用。在这里，我们研究了天然衍生物蛇床子素作为一种有前途的抗卵巢癌化合物，并评估了其抑制和消除肿瘤进展的能力。此外，我们发现了内质网-线粒体轴介导的蛇床子素对 ES2 和 OV90 卵巢癌细胞的抗癌机制，并证明了其钙依赖性药理学潜力。在机制上，发现蛇床子素靶向磷脂酰肌醇 3-激酶/丝裂原活化蛋白激酶信号通路，以促进卵巢癌的肿瘤抑制。此外，我们使用斑马鱼异种移植试验确定了蛇床子素在三维肿瘤形成模型中的作用，为蛇床素素在不依赖锚定的肿瘤微环境中的药理作用提供了令人信服的证据。这些发现表明，蛇床子素作为靶向卵巢癌的药物具有强大的潜力。

更新日期：2020-07-22

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