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Article Publish Status: FREE
Abstract Title:

Neferine induces autophagy-dependent cell death in apoptosis-resistant cancers via ryanodine receptor and Ca-dependent mechanism.

Abstract Source:

Sci Rep. 2019 Dec 27 ;9(1):20034. Epub 2019 Dec 27. PMID: 31882989

Abstract Author(s):

Betty Yuen Kwan Law, Francesco Michelangeli, Yuan Qing Qu, Su-Wei Xu, Yu Han, Simon Wing Fai Mok, Ivo Ricardo de Seabra Rodrigues Dias, Masood-Ul-Hassan Javed, Wai-Kit Chan, Wei-Wei Xue, Xiao-Jun Yao, Wu Zeng, Hui Zhang, Jing-Rong Wang, Liang Liu, Vincent Kam Wai Wong

Article Affiliation:

Betty Yuen Kwan Law

Abstract:

Resistance 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.

Study Type : In Vitro Study

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