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dc.contributor.authorLaw, Betty Yuen Kwan
dc.contributor.authorMichelangeli, Francesco
dc.contributor.authorQu, Yuan Qing; orcid: 0000-0003-3733-3661
dc.contributor.authorXu, Su-Wei
dc.contributor.authorHan, Yu
dc.contributor.authorMok, Simon Wing Fai
dc.contributor.authorDias, Ivo Ricardo De Seabra Rodrigues
dc.contributor.authorJaved, Masood-Ul-Hassan
dc.contributor.authorChan, Wai-Kit
dc.contributor.authorXue, Wei-Wei
dc.contributor.authorYao, Xiao-Jun
dc.contributor.authorZeng, Wu
dc.contributor.authorZhang, Hui
dc.contributor.authorWang, Jing-Rong
dc.contributor.authorLiu, Liang; email: lliu@must.edu.mo
dc.contributor.authorWong, Vincent Kam Wai; orcid: 0000-0002-2951-8108; email: bowaiwong@gmail.com
dc.date.accessioned2020-01-11T01:42:04Z
dc.date.available2020-01-11T01:42:04Z
dc.date.issued2019-12-27
dc.date.submitted2019-06-28
dc.identifierpubmed: 31882989
dc.identifierdoi: 10.1038/s41598-019-56675-6
dc.identifierpii: 10.1038/s41598-019-56675-6
dc.identifierpmc: PMC6934498
dc.identifier.citationScientific reports, volume 9, issue 1, page 20034
dc.identifier.urihttp://hdl.handle.net/10034/623058
dc.descriptionFrom PubMed via Jisc Publications Router
dc.descriptionHistory: received 2019-06-28, accepted 2019-12-16
dc.descriptionPublication status: epublish
dc.description.abstractResistance of cancer cells to chemotherapy is a significant clinical concern and mechanisms regulating cell death in cancer therapy, including apoptosis, autophagy or necrosis, have been extensively investigated over the last decade. Accordingly, the identification of medicinal compounds against chemoresistant cancer cells via new mechanism of action is highly desired. Autophagy is important in inducing cell death or survival in cancer therapy. Recently, novel autophagy activators isolated from natural products were shown to induce autophagic cell death in apoptosis-resistant cancer cells in a calcium-dependent manner. Therefore, enhancement of autophagy may serve as additional therapeutic strategy against these resistant cancers. By computational docking analysis, biochemical assays, and advanced live-cell imaging, we identified that neferine, a natural alkaloid from Nelumbo nucifera, induces autophagy by activating the ryanodine receptor and calcium release. With well-known apoptotic agents, such as staurosporine, taxol, doxorubicin, cisplatin and etoposide, utilized as controls, neferine was shown to induce autophagic cell death in a panel of cancer cells, including apoptosis-defective and -resistant cancer cells or isogenic cancer cells, via calcium mobilization through the activation of ryanodine receptor and Ulk-1-PERK and AMPK-mTOR signaling cascades. Taken together, this study provides insights into the cytotoxic mechanism of neferine-induced autophagy through ryanodine receptor activation in resistant cancers.
dc.languageeng
dc.sourceeissn: 2045-2322
dc.titleNeferine induces autophagy-dependent cell death in apoptosis-resistant cancers via ryanodine receptor and Ca
dc.typearticle
dc.date.updated2020-01-11T01:42:04Z
dc.date.accepted2019-12-16


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