曲普奈德通过激活 p38/p53 通路和自噬诱导卵巢癌细胞凋亡并抑制其增殖

IF 3.3 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Bioorganic & Medicinal Chemistry Pub Date : 2024-08-01 DOI:10.1016/j.bmc.2024.117788
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引用次数: 0

摘要

卵巢癌是女性常见的恶性肿瘤,70%的卵巢癌患者确诊时已是晚期。药物化疗是治疗卵巢癌的重要方法,但复发和化疗耐药往往导致治疗失败。在这项研究中,我们筛选了传统中草药三尖杉的 10 种提取物,发现三尖杉内酯具有很强的抗卵巢癌活性,对 A2780 细胞株的 IC50 值仅为 3.803 nM。此外,我们还确定,在体外,三氪苷对 A2780 细胞株的抗肿瘤效果优于铂类化疗药物,而且三氪苷在体内没有明显的副作用。我们发现,三苯氧胺通过激活 p38/p53 通路诱导卵巢癌细胞凋亡,还能诱导细胞周期停滞在 S 期。此外,我们还证明三苯氧胺能激活致死性自噬,导致卵巢癌细胞生长受抑制和细胞死亡,从而产生抗卵巢癌作用。三苯氧胺通过激活 p38/p53 通路和诱导自噬促进细胞凋亡发挥抗卵巢癌作用,为卵巢癌的治疗提供了一种新的候选药物和策略。
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Triptonide induces apoptosis and inhibits the proliferation of ovarian cancer cells by activating the p38/p53 pathway and autophagy

Ovarian cancer is a common malignant tumor in women, and 70 % of ovarian cancer patients are diagnosed at an advanced stage. Drug chemotherapy is an important method for treating ovarian cancer, but recurrence and chemotherapy resistance often lead to treatment failure. In this study, we screened 10 extracts of Tripterygium wilfordii, a traditional Chinese herb, and found that triptonide had potent anti-ovarian cancer activity and an IC50 of only 3.803 nM against A2780 cell lines. In addition, we determined that triptonide had a better antitumor effect on A2780 cell lines than platinum chemotherapeutic agents in vitro and that triptonide had no significant side effects in vivo. We found that triptonide induced apoptosis in ovarian cancer cells through activation of the p38/p53 pathway and it also induced cell cycle arrest at the S phase. In addition, we demonstrated that triptonide could activate lethal autophagy, which led to growth inhibition and cell death in ovarian cancer cells, resulting in an anti-ovarian cancer effect. Triptonide exerts its anti-ovarian cancer effect through activation of the p38/p53 pathway and induction of autophagy to promote apoptosis, which provides a new candidate drug and strategy for the treatment of ovarian cancer.

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来源期刊
Bioorganic & Medicinal Chemistry
Bioorganic & Medicinal Chemistry 医学-生化与分子生物学
CiteScore
6.80
自引率
2.90%
发文量
413
审稿时长
17 days
期刊介绍: Bioorganic & Medicinal Chemistry provides an international forum for the publication of full original research papers and critical reviews on molecular interactions in key biological targets such as receptors, channels, enzymes, nucleotides, lipids and saccharides. The aim of the journal is to promote a better understanding at the molecular level of life processes, and living organisms, as well as the interaction of these with chemical agents. A special feature will be that colour illustrations will be reproduced at no charge to the author, provided that the Editor agrees that colour is essential to the information content of the illustration in question.
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