Induction of ferroptosis in human nasopharyngeal cancer cells by cucurbitacin B: molecular mechanism and therapeutic potential.
Induction of ferroptosis in human nasopharyngeal cancer cells by cucurbitacin B: molecular mechanism and therapeutic potential.
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葫芦素 B 诱导人鼻咽癌细胞铁死亡的分子机制和治疗潜力
DOI：
10.1038/s41419-021-03516-y
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发表时间：
2021-03-04
影响因子：
9
通讯作者：
Liang B
中科院分区：
文献类型：
--
作者：
Huang S;Cao B;Zhang J;Feng Y;Wang L;Chen X;Su H;Liao S;Liu J;Yan J;Liang B
葫芦素 B (CuB) 是一种广泛使用的三萜类分子，具有多种生物活性。以往关于CuB抗肿瘤机制的研究多集中在细胞凋亡方面，而其诱导铁死亡作用的研究鲜有报道。在此，我们首次发现了CuB对人鼻咽癌细胞的优异细胞毒性，并阐明了其潜在的铁死亡诱导机制。通过透射电子显微镜观察到的线粒体超微结构的形态变化表明，CuB 处理的细胞发生铁死亡。 CuB 引起细胞内铁离子的积累和谷胱甘肽的消耗。详细的分子机制研究证实，CuB 既诱导广泛的脂质过氧化，又下调 GPX4 的表达，最终启动铁死亡的多管齐下机制。此外，CuB 通过抑制细胞微管聚合、阻滞细胞周期、抑制迁移和侵袭而在体外表现出抗肿瘤作用。最后，CuB 显着抑制肿瘤进展，且在体内没有引起明显的副作用。总而言之，我们的研究强调了 CuB 作为鼻咽癌铁死亡诱导剂的治疗潜力，并为开发具有源自天然产物的新颖分子机制的有效抗肿瘤药物提供了宝贵的见解。
Cucurbitacin B (CuB) is a widely available triterpenoid molecule that exhibits various biological activities. Previous studies on the anti-tumour mechanism of CuB have mostly focused on cell apoptosis, and research on the ferroptosis-inducing effect has rarely been reported. Herein, we first discovered the excellent cytotoxicity of CuB towards human nasopharyngeal carcinoma cells and elucidated its potential ferroptosis-inducing mechanisms. Morphology alterations of mitochondrial ultrastructure, as observed via transmission electron microscopy, showed that CuB-treated cells undergo ferroptosis. CuB caused intracellular accumulation of iron ions and depletion of glutathione. Detailed molecular mechanism investigation confirmed that CuB both induced widespread lipid peroxidation and downregulated the expression of GPX4, ultimately initiating a multipronged mechanism of ferroptosis. Furthermore, CuB exhibited anti-tumour effects in vitro by inhibiting cellular microtubule polymerization, arresting cell cycle and suppressing migration and invasion. Finally, CuB significantly inhibited tumour progression without causing obvious side effects in vivo. Altogether, our study highlighted the therapeutic potential of CuB as a ferroptosis-inducing agent for nasopharyngeal cancer, and it provided valuable insights for developing effective anti-tumour agents with novel molecular mechanisms derived from natural products.
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影响因子：
64.5
作者：
Dixon SJ;Lemberg KM;Lamprecht MR;Skouta R;Zaitsev EM;Gleason CE;Patel DN;Bauer AJ;Cantley AM;Yang WS;Morrison B 3rd;Stockwell BR
通讯作者：
Stockwell BR
影响因子：
14.8
作者：
Gaschler MM;Andia AA;Liu H;Csuka JM;Hurlocker B;Vaiana CA;Heindel DW;Zuckerman DS;Bos PH;Reznik E;Ye LF;Tyurina YY;Lin AJ;Shchepinov MS;Chan AY;Peguero-Pereira E;Fomich MA;Daniels JD;Bekish AV;Shmanai VV;Kagan VE;Mahal LK;Woerpel KA;Stockwell BR
通讯作者：
Stockwell BR
三萜乙醇素B增强了人类乳腺癌化学疗法的抗增殖活性。
影响因子：
6.4
作者：
Aribi, Ahmed;Gery, Sigal;Lee, Dhong Hyun;Thoennissen, Nils H.;Thoennissen, Gabriela B.;Alvarez, Rocio;Quoc Ho;Lee, Kunik;Doan, Ngan B.;Chan, Kin T.;Toh, Melvin;Said, Jonathan W.;Koeffler, H. Phillip
通讯作者：
Koeffler, H. Phillip
影响因子：
9
作者：
Park, Tae-Jun;Park, Jei Hyoung;Lee, Sang Chul
通讯作者：
Lee, Sang Chul
影响因子：
9.7
作者：
Chan, Kin Tak;Li, Kwan;Xie, Wei Dong
通讯作者：
Xie, Wei Dong