{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:14:35Z","timestamp":1790774075447,"version":"4.1.0"},"reference-count":29,"publisher":"Wiley","issue":"21","license":[{"start":{"date-parts":[[2020,9,25]],"date-time":"2020-09-25T00:00:00Z","timestamp":1600992000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["41576160"],"award-info":[{"award-number":["41576160"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["41776140"],"award-info":[{"award-number":["41776140"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Breast cancer is the leading cause of death among women with malignant tumors worldwide. Bone metastasis is the main factor affecting the prognosis of breast cancer. Therefore, both antitumor and anti\u2010breast\u2010cancer\u2010induced osteolysis agents are urgently needed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We examined the effect of Asperolide A (AA), a marine\u2010derived agent, on osteolysis and RANKL\u2010induced phosphoinositide 3\u2010kinase (PI3K)\/AKT\/mTOR\/c\u2010FOS\/nuclear factor\u2010activated T cell 1 (NFATc1) pathway activation, F\u2010actin ring formation, and reactive oxygen species (ROS) generation in vitro. We evaluated AA effect on breast cancer MDA\u2010MB\u2010231 and MDA\u2010MB\u2010436 cells in vitro through CCK8 assay, wound healing assay, transwell assay, Annexin V\u2010FITC\/PI staining for cell apoptosis, and cell cycle assay. Furthermore, we assessed the effect of AA in vivo using a breast cancer\u2010induced bone osteolysis nude mouse model, followed by micro\u2010computed tomography, tartrate\u2010resistant acid phosphatase staining, and hematoxylin and eosin staining.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Asperolide A inhibited osteoclast formation and differentiation, bone resorption, F\u2010actin belt formation, ROS activity, and osteoclast\u2010specific gene and protein expressions and prevented PI3K\/AKT\/mTOR\/c\u2010FOS\/NFATc1 signaling activation in a dose\u2010dependent manner in vitro. AA also inhibited breast cancer growth and breast cancer\u2010induced bone osteolysis by reducing osteoclast formation and function and inactivated PI3K\/AKT\/mTOR signaling in vivo.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our study demonstrated that AA suppressed bone metastatic breast cancer. These findings indicate AA as a potential, novel curative drug candidate for patients with bone metastatic breast cancer.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.3432","type":"journal-article","created":{"date-parts":[[2020,9,25]],"date-time":"2020-09-25T16:33:26Z","timestamp":1601051606000},"page":"8173-8185","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Asperolide A prevents bone metastatic breast cancer via the PI3K\/AKT\/mTOR\/c\u2010Fos\/NFATc1 signaling pathway"],"prefix":"10.1002","volume":"9","author":[{"given":"Wenli","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology College of Basic Medical Navy Medical University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youlutuziayi","family":"Rixiati","sequence":"additional","affiliation":[{"name":"Department of Pathology Soochow University Medical School Suzhou 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