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Conventional chemotherapeutic agent\u2010induced adverse events, including toxicity, neuropathy or drug resistance, significantly decrease the patients' quality of life and can even lead to interruption of treatment. Therefore, novel therapeutic drugs and strategies are urgently needed to improve MM therapy and patient outcomes. Here, we show that solamargine (SM), a steroidal alkaloid glycoside isolated from a Chinese herb <jats:italic>Solanum nigrum L<\/jats:italic>., exhibits promising anti\u2010MM activity. In particular, SM suppressed the viability of MM cell lines (ARP\u20101 and NCI\u2010H929) in a concentration\u2010 and time\u2010dependent manner, inducing apoptosis in these cells. RNA\u2010seq analysis showed that treatment with SM led to the upregulation of genes associated with cell death and autophagy in H929 cells. Further, we found that treatment with SM activated autophagy in the MM cells, as incubation with 3\u2010Methyladenine, an inhibitor of autophagy, significantly alleviated SM\u2010triggered apoptosis and inhibition of viability in MM cells. Interestingly, we also observed a synergistic effect between SM and bortezomib (BTZ), a common chemotherapeutic agent for MM, in both MM cells and human bone marrow CD138+ primary myeloma cells. We also confirmed the single\u2010agent efficacy of SM and the synergistic effects between SM and BTZ in an MM xenograft mouse model. Collectively, these findings indicate that SM exerts an anti\u2010MM effect, at least in part, by activating cell autophagy and reveal that SM alone or in combination with BTZ is a potential therapeutic strategy for treating MM.<\/jats:p>","DOI":"10.1111\/1440-1681.13643","type":"journal-article","created":{"date-parts":[[2022,3,16]],"date-time":"2022-03-16T15:05:40Z","timestamp":1647443140000},"page":"674-685","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Solamargine induces autophagy\u2010mediated apoptosis and enhances bortezomib activity in multiple myeloma"],"prefix":"10.1111","volume":"49","author":[{"given":"Qiaoyan","family":"Han","sequence":"first","affiliation":[{"name":"Department of Hematology Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine  Nanjing China"},{"name":"Department of Hematology Jingjiang People's Hospital  Jingjiang 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