ent-Kaurane diterpenoids induce apoptosis and ferroptosis through targeting redox resetting to overcome cisplatin resistance.
ent-Kaurane diterpenoids induce apoptosis and ferroptosis through targeting redox resetting to overcome cisplatin resistance.
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对映贝壳杉烷二萜类化合物通过靶向氧化还原重置来克服顺铂耐药性，诱导细胞凋亡和铁死亡
DOI：
10.1016/j.redox.2021.101977
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发表时间：
2021-07
期刊：
影响因子：
11.4
通讯作者：
Lou H
中科院分区：
文献类型：
--
作者：
Sun Y;Qiao Y;Liu Y;Zhou J;Wang X;Zheng H;Xu Z;Zhang J;Zhou Y;Qian L;Zhang C;Lou H
活性氧（reactive oxygen species，ROS）诱导是许多化疗药物杀伤肿瘤细胞的有效机制，而抗癌药物诱导的氧化还原稳态失调会促进肿瘤的耐药性。天然贝壳杉烷型二萜类化合物可与谷胱甘肽（GSH）和抗氧化酶中的巯基共价结合，破坏细胞内氧化还原稳态。因此，对映贝壳杉烷二萜类化合物的氧化还原重置破坏可能成为癌症治疗的可行策略。本研究从中国地钱中分离得到30个对映贝壳杉烷型二萜类化合物，其中包括20个新样品，并通过氧化还原重置破坏研究了它们的特异靶点及其在肿瘤耐药中的可能应用。11 β-hydroxy-ent-16-kaurene-15-one（23）对多种癌细胞系具有较强的抑制活性。此外，化合物23通过增加HepG2细胞中的细胞ROS水平诱导细胞凋亡和铁凋亡。由化合物23诱导的ROS积累是通过靶向过氧化物氧还蛋白I/II（Prdx I/II）和GSH消耗抑制抗氧化系统引起的。此外，化合物23通过诱导细胞凋亡和铁凋亡在体外和体内敏化顺铂（CDDP）抗性A549/CDDP癌细胞。因此，对映贝壳杉烷衍生物显示出在癌症化疗中通过Prdx I/II和GSH的双重抑制通过氧化还原重置破坏敏化CDDP抗性的潜在应用。从中国苔类植物Jungermannia tetragona中分离得到30个对映贝壳杉烷型二萜化合物。首次发现11 β-hydroxy-ent-16-kaurene-15-one（23）具有诱导细胞凋亡和铁凋亡的作用。化合物23可通过直接靶向Prdx I/II和GSH来扰乱细胞内氧化还原系统。化合物23可通过氧化还原重置破坏而在体内外敏化A549/CDDP癌细胞。
Reactive oxygen species (ROS) induction is an effective mechanism to kill cancer cells for many chemotherapeutics, while resettled redox homeostasis induced by the anticancer drugs will promote cancer chemoresistance. Natural ent-kaurane diterpenoids have been found to bind glutathione (GSH) and sulfhydryl group in antioxidant enzymes covalently, which leads to the destruction of intracellular redox homeostasis. Therefore, redox resetting destruction by ent-kaurane diterpenoids may emerge as a viable strategy for cancer therapy. In this study, we isolated 30 ent-kaurane diterpenoids including 20 new samples from Chinese liverworts Jungermannia tetragona Lindenb and studied their specific targets and possible application in cancer drug resistance through redox resetting destruction. 11β-hydroxy-ent-16-kaurene-15-one (23) possessed strong inhibitory activity against several cancer cell lines. Moreover, compound 23 induced both apoptosis and ferroptosis through increasing cellular ROS levels in HepG2 cells. ROS accumulation induced by compound 23 was caused by inhibition of antioxidant systems through targeting peroxiredoxin I/II (Prdx I/II) and depletion of GSH. Furthermore, compound 23 sensitized cisplatin (CDDP)-resistant A549/CDDP cancer cells in vitro and in vivo by inducing apoptosis and ferroptosis. Thus, the ent-kaurane derivative showed potential application for sensitizing CDDP resistance by redox resetting destruction through dual inhibition of Prdx I/II and GSH in cancer chemotherapy. Thirty ent-kaurane diterpenoids were isolated from the Chinese liverworts, Jungermannia tetragona. 11β-hydroxy-ent-16-kaurene-15-one (23) was identified to induce apoptosis and ferroptosis for the first time. Compound 23 could disorder the intracellular redox system by directly targeting Prdx I/II and GSH. Compound 23 could sensitize A549/CDDP cancer cells in vitro and in vivo through redox resetting destruction.
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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
DOI：
10.1038/nri3423
发表时间：
2013-05
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
金诺芬通过调节 ROS 和糖酵解消除干细胞样癌细胞副群。
影响因子：
9
作者：
Hou GX;Liu PP;Zhang S;Yang M;Liao J;Yang J;Hu Y;Jiang WQ;Wen S;Huang P
通讯作者：
Huang P
Adenanthin 靶向过氧化还原蛋白 I 和 II 诱导白血病细胞分化
影响因子：
14.8
作者：
Liu, Chuan-Xu;Yin, Qian-Qian;Chen, Guo-Qiang
通讯作者：
Chen, Guo-Qiang
影响因子：
5.1
作者：
Piska, Kamil;Koczurkiewicz, Paulina;Pekala, Elzbieta
通讯作者：
Pekala, Elzbieta