Solamargine induces autophagy-mediated apoptosis and enhances bortezomib activity in multiple myeloma.
Solamargine induces autophagy-mediated apoptosis and enhances bortezomib activity in multiple myeloma.
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DOI：
10.1111/1440-1681.13643
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发表时间：
2022-06
影响因子：
2.9
通讯作者：
Chen, Bing
中科院分区：
文献类型：
--
作者：
Han, Qiaoyan;Bai, Hua;Xu, Yong;Zhou, Min;Zhou, He;Dong, Xiaoqing;Chen, Bing
多发性骨髓瘤（MM）是一种无法治愈的浆细胞恶性肿瘤，生存率很低。传统化疗药物引起的不良事件，包括毒性、神经病变或耐药性，显着降低患者的生活质量，甚至可能导致治疗中断。因此，迫切需要新的治疗药物和策略来改善 MM 治疗和患者预后。在这里，我们发现，从中草药 Solanum nigrum L. 中分离出来的 solamargine (SM) 是一种甾体生物碱苷，具有良好的抗 MM 活性。特别是，SM 以浓度和时间依赖性方式抑制 MM 细胞系（ARP-1 和 NCI-H929）的活力，诱导这些细胞凋亡。 RNA-seq 分析表明，SM 治疗导致 H929 细胞中与细胞死亡和自噬相关的基因上调。此外，我们发现，用 SM 治疗可激活 MM 细胞中的自噬，与自噬抑制剂 3-甲基腺嘌呤一起孵育，可显着减轻 SM 触发的细胞凋亡和对 MM 细胞活力的抑制。有趣的是，我们还在 MM 细胞和人骨髓 CD138+ 原发性骨髓瘤细胞中观察到 SM 和硼替佐米 (BTZ)（一种常见的 MM 化疗药物）之间的协同作用。我们还在多发性骨髓瘤异种移植小鼠模型中证实了 SM 的单药疗效以及 SM 和 BTZ 之间的协同作用。总的来说，这些发现表明 SM 至少部分通过激活细胞自噬发挥抗 MM 作用，并揭示 SM 单独或与 BTZ 组合是治疗 MM 的潜在治疗策略。
Multiple myeloma (MM) is an incurable plasma cell malignancy with a poor survival rate. Conventional chemotherapeutic agent‐induced 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 Solanum nigrum L., exhibits promising anti‐MM activity. In particular, SM suppressed the viability of MM cell lines (ARP‐1 and NCI‐H929) in a concentration‐ and time‐dependent manner, inducing apoptosis in these cells. RNA‐seq 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‐Methyladenine, an inhibitor of autophagy, significantly alleviated SM‐triggered 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‐agent 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‐MM 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.
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影响因子：
3.3
作者：
Carew JS;Kelly KR;Nawrocki ST
通讯作者：
Nawrocki ST
Lycorine 下调 HMGB1 以抑制自噬并增强多发性骨髓瘤中硼替佐米的活性
影响因子：
12.4
作者：
Roy M;Liang L;Xiao X;Peng Y;Luo Y;Zhou W;Zhang J;Qiu L;Zhang S;Liu F;Ye M;Zhou W;Liu J
通讯作者：
Liu J
影响因子：
5
作者：
Desantis V;Saltarella I;Lamanuzzi A;Mariggiò MA;Racanelli V;Vacca A;Frassanito MA
通讯作者：
Frassanito MA
影响因子：
5.8
作者：
Al Sinani SS;Eltayeb EA;Coomber BL;Adham SA
通讯作者：
Adham SA
影响因子：
4
作者：
Kazandjian D
通讯作者：
Kazandjian D