A Novel Synthesized Cyclohexane-Hydroxytyrosol Derivative Suppresses Ovarian Cancer Cell Growth Through Inducing Reactive Oxidative Species and Blocking Autophagic Flux.

IF 5.9 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Antioxidants & redox signaling Pub Date : 2024-09-01 Epub Date: 2024-03-27 DOI:10.1089/ars.2023.0400
Guanfei Zhang, Min Wang, Yilin Gao, Aikaterini Christina Komianou, Eleftheria A Georgiou, Yan Wang, Yezi Zheng, Jiankang Liu, Ioannis K Kostakis, Lin Zhao
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一种新合成的环己烷-羟基酪醇衍生物通过诱导 ROS 和阻断自噬通量抑制卵巢癌细胞的生长。
目的:卵巢癌(OC)细胞的耐药性往往导致卵巢癌患者复发、转移和高死亡率。据报道,羟基酪醇(HT)可抑制卵巢癌和其他类型癌细胞的增殖。在此,我们合成了一种新型环己烷-羟基酪醇衍生物(Chx-HT),以增强抗癌药物的疗效。我们考察了 Chx-HT 在体外和异种移植小鼠模型中对 OC 细胞的生长抑制作用,并研究了其潜在机制:结果:我们发现 Chx-HT 在体外和体内都能抑制细胞增殖、促进细胞凋亡、通过减少脂肪酸β-氧化重塑葡萄糖和脂质代谢,同时增加糖酵解、新脂肪酸合成和脂滴积累、损害线粒体呼吸并诱导氧化应激。此外,Chx-HT 在晚期通过阻碍溶酶体酪蛋白的成熟来阻断自噬通量,但也会在能量不足时通过 p-AMPK/p-mTOR/p-ULK1 途径激活自噬:ROS在介导Chx-HT对卵巢癌细胞增殖、凋亡、自噬、TCA循环、FAO和线粒体呼吸的影响中起着关键作用,而自噬激活是Chx-HT对卵巢癌细胞糖酵解、新脂肪酸合成和脂滴积累的影响的基础。用Chx-HT和自噬抑制剂或糖酵解抑制剂共处理卵巢癌细胞会产生相加的增殖抑制作用。我们的研究表明,Chx-HT 通过抑制 ROS 和自噬介导的代谢重塑,是一种很有前景的卵巢癌治疗药物。
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来源期刊
Antioxidants & redox signaling
Antioxidants & redox signaling 生物-内分泌学与代谢
CiteScore
14.10
自引率
1.50%
发文量
170
审稿时长
3-6 weeks
期刊介绍: Antioxidants & Redox Signaling (ARS) is the leading peer-reviewed journal dedicated to understanding the vital impact of oxygen and oxidation-reduction (redox) processes on human health and disease. The Journal explores key issues in genetic, pharmaceutical, and nutritional redox-based therapeutics. Cutting-edge research focuses on structural biology, stem cells, regenerative medicine, epigenetics, imaging, clinical outcomes, and preventive and therapeutic nutrition, among other areas. ARS has expanded to create two unique foci within one journal: ARS Discoveries and ARS Therapeutics. ARS Discoveries (24 issues) publishes the highest-caliber breakthroughs in basic and applied research. ARS Therapeutics (12 issues) is the first publication of its kind that will help enhance the entire field of redox biology by showcasing the potential of redox sciences to change health outcomes. ARS coverage includes: -ROS/RNS as messengers -Gaseous signal transducers -Hypoxia and tissue oxygenation -microRNA -Prokaryotic systems -Lessons from plant biology
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