Eucannabinolide, a novel sesquiterpene lactone, suppresses the growth, metastasis and BCSCS-like traits of TNBC via inactivation of STAT3.
Eucannabinolide, a novel sesquiterpene lactone, suppresses the growth, metastasis and BCSCS-like traits of TNBC via inactivation of STAT3.
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真大麻素内酯是一种新型倍半萜内酯，通过灭活 STAT3 来抑制 TNBC 的生长、转移和 BCSCS 样特征
DOI：
10.1016/j.neo.2020.10.012
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发表时间：
2021-01
期刊：
影响因子：
--
通讯作者：
Zhao H
中科院分区：
文献类型：
--
作者：
Zhu Z;Yuan J;Xu X;Wei Y;Yang B;Zhao H
Euc降低p-STAT3 （Tyr705）的表达、核易位和dna结合。Euc通过抑制STAT3抑制细胞活力、转移和bcsc样性状。Euc通过Michael加成反应与STAT3共价相互作用。Euc表现出有效的抗肿瘤生长和肺转移，无急性毒性。转录激活因子3 （STAT3）是三阴性乳腺癌（TNBC）治疗的重要靶点。在本研究中，我们旨在研究从大麻泽兰中分离的新型倍半萜内酯桉叶大麻素内酯（Eucannabinolide, Euc）的潜在活性。通过靶向STAT3来治疗TNBC，并期望Euc将作为STAT3的抑制剂用于治疗TNBC。我们发现Euc有效抑制STAT3在酪氨酸705位点的激活，抑制其向细胞核的易位，降低其DNA结合能力。此外，引入STAT3短发夹rna或STAT3抑制剂sgi -201可减弱eucc诱导的细胞活力抑制。Euc抑制细胞活力、增殖、转移和乳腺癌干细胞样特性，但不诱导人乳腺上皮细胞的细胞毒性。体内研究同样表明，给药Euc抑制异种移植肿瘤的生长，并损害肺转移模型的肿瘤转移。上述现象与Euc诱导的STAT3功能障碍有关。综上所述，Euc通过靶向STAT3在TNBC中发挥抗增殖、抗转移和抗乳腺癌干细胞样特性的作用。这些数据强调，Euc作为STAT3抑制剂的发展可能为TNBC提供一种有希望的治疗策略。
Euc decreased expression of p-STAT3 (Tyr705), nuclear translocation and DNA-binding. Euc inhibited cell viability, metastasis and BCSC-like traits by inhibiting STAT3. Euc covalently interacted with STAT3 through a Michael addition reaction. Euc exhibits potent anti-tumor growth and lung metastasis without acute toxicity. Signal transducer and activator of transcription 3 (STAT3) is an important therapeutic target to triple negative breast cancer (TNBC) treatment. In the present study, we aim to investigate the potential activity of Eucannabinolide (Euc), a novel sesquiterpene lactone separated from Eupatorium cannabinum Linn. against TNBC by targeting STAT3 and expect that Euc will be developed as an inhibitor of STAT3 in the treatment of TNBC. We found that Euc effectively suppressed STAT3 activation at tyrosine 705, inhibited its translocation to nucleus, and decreased its DNA binding capacity. Moreover, introduction of STAT3-short hairpin RNAs or STAT3 inhibitor S3I-201 attenuates the Euc-induced inhibition of cell viability. And, Euc inhibited cell viability, proliferation, metastasis and breast cancer stem cell-like traits but did not induce cytotoxicity in human mammary epithelial cells. The in vivo study similarly demonstrated that administration of Euc inhibited the growth of xenograft tumors and impaired tumor metastasis of a lung metastasis model. The above phenomena were associated with STAT3 dysfunction induced by Euc. In conclusion, Euc elicits the effects of anti-proliferation, anti-metastasis and anti-breast cancer stem cell-like traits in TNBC via targeting STAT3. These data highlight that development of Euc as a STAT3 inhibitor may offer a promising therapeutic strategy for TNBC.
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影响因子：
4.7
作者：
Abubaker K;Luwor RB;Escalona R;McNally O;Quinn MA;Thompson EW;Findlay JK;Ahmed N
通讯作者：
Ahmed N
影响因子：
50.3
作者：
Bai, Longchuan;Zhou, Haibin;Wang, Shaomeng
通讯作者：
Wang, Shaomeng
影响因子：
20.3
作者：
Xiang, Michael;Kim, Haesook;Frank, David A.
通讯作者：
Frank, David A.
影响因子：
6.4
作者：
Banerjee K;Resat H
通讯作者：
Resat H
Eupalinolide J 通过靶向 STAT3 信号通路抑制三阴性乳腺癌细胞的生长
影响因子：
5.6
作者：
Lou, Chenghua;Chen, Yan;Zhao, Huajun
通讯作者：
Zhao, Huajun