隐托拉平类似物通过靶向细胞生长、氧化应激和 PTEN/Akt/mTOR 信号通路对小鼠艾氏腹水癌细胞表现出抗肿瘤活性

IF 2.6 4区 医学 Q3 CHEMISTRY, MEDICINAL Anti-cancer agents in medicinal chemistry Pub Date : 2024-02-02 DOI:10.2174/0118715206274318231128072821
Bishoy El-Aarag, Eman S. Shalaan, Abdullah A.S. Ahmed, Ibrahim El Tantawy El Sayed, Wafaa M. Ibrahim
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引用次数: 0

摘要

背景:由于相关毒性和化疗耐药性,化疗的疗效仍然有限。因此,合成和研究可能消除这些限制的新型癌症治疗药物势在必行。研究目的本研究旨在探讨隐托拉平(CPE)类似物对小鼠艾氏腹水癌细胞(EACs)的抗癌效力。研究方法评估 CPE 类似物对 EAC 细胞活力和腹水体积的影响,以及对丙二醛、总抗氧化能力和过氧化氢酶的影响。还测量了 EAC 细胞中 Caspase-8 和 mTOR 的浓度,并测定了 PTEN 和 Akt 的表达水平。结果显示结果表明,CPE 类似物对 EAC 细胞活力具有细胞毒性作用,并能减少腹水体积。此外,该类似物通过增加丙二醛水平、降低总抗氧化能力和过氧化氢酶活性水平诱导 EAC 细胞氧化应激。它还通过提高 EAC 中 caspase-8 的浓度诱导细胞凋亡。此外,它还会降低 EAC 中 mTOR 的浓度。此外,它还能上调 EAC 中 PTEN 的表达,下调 Akt 的表达:结果表明,CPE 类似物对 EAC 细胞活力具有细胞毒性作用,并能减少腹水体积。此外,该类似物通过增加丙二醛水平、降低总抗氧化能力和过氧化氢酶活性水平,诱导 EAC 细胞氧化应激。它还通过提高 EAC 中 caspase-8 的浓度诱导细胞凋亡。此外,它还会降低 EAC 中 mTOR 的浓度。此外,它还能上调 EAC 中 PTEN 的表达,下调 Akt 的表达。结论我们的研究结果表明,CPE 类似物对小鼠 EACs 的抗癌活性是通过调节 PTEN/Akt/mTOR 信号通路介导的:我们的研究结果表明,新CPE类似物对小鼠EACs的抗癌活性是通过调节PTEN/Akt/mTOR信号通路介导的。
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Cryptolepine Analog exhibits Antitumor Activity against Ehrlich Ascites Carcinoma Cells in Mice via Targeting Cell Growth, Oxidative Stress, and PTEN/Akt/mTOR Signaling Pathway
Background: The efficacy of chemotherapy continues to be limited due to associated toxicity and chemoresistance. Thus, synthesizing and investigating novel agents for cancer treatment that could potentially eliminate such limitations is imperative. Objective: The current study aims to explore the anticancer potency of cryptolepine (CPE) analog on Ehrlich ascites carcinoma cells (EACs) in mice. Methods: The effect of a CPE analog on EAC cell viability and ascites volume, as well as malonaldehyde, total antioxidant capacity, and catalase, were estimated. The concentration of caspase-8 and mTOR in EACs was also measured, and the expression levels of PTEN and Akt were determined. Results: Results revealed that CPE analog exerts a cytotoxic effect on EAC cell viability and reduces the ascites volume. Moreover, this analog induces oxidative stress in EACs by increasing the level of malonaldehyde and decreasing the level of total antioxidant capacity and catalase activity. It also induces apoptosis by elevating the concentration of caspase-8 in EACs. Furthermore, it decreases the concentration of mTOR in EACs. Moreover, it upregulates the expression of PTEN and downregulates the expression of Akt in EACs. result: Results revealed that CPE analog exerts a cytotoxic effect on EAC cell viability and reduces the ascites volume. Moreover, this analog induces oxidative stress in EACs by increasing the level of malonaldehyde and decreasing the level of total antioxidant capacity and catalase activity. It also induces apoptosis by elevating the concentration of caspase-8 in EACs. Furthermore, it decreases the concentration of mTOR in EACs. Moreover, it upregulates the expression of PTEN and downregulates the expression of Akt in EACs. Conclusion: Our findings showed the anticancer activity of CPE analog against EACs in mice mediated by regulation of the PTEN/Akt/mTOR signaling pathway. conclusion: Our findings showed the anticancer activity of newly CPE analog against EACs in mice mediated by regulation of PTEN/Akt/mTOR signaling pathway.
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来源期刊
Anti-cancer agents in medicinal chemistry
Anti-cancer agents in medicinal chemistry ONCOLOGY-CHEMISTRY, MEDICINAL
CiteScore
5.10
自引率
3.60%
发文量
323
审稿时长
4-8 weeks
期刊介绍: Formerly: Current Medicinal Chemistry - Anti-Cancer Agents. Anti-Cancer Agents in Medicinal Chemistry aims to cover all the latest and outstanding developments in medicinal chemistry and rational drug design for the discovery of anti-cancer agents. Each issue contains a series of timely in-depth reviews and guest edited issues written by leaders in the field covering a range of current topics in cancer medicinal chemistry. The journal only considers high quality research papers for publication. Anti-Cancer Agents in Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments in cancer drug discovery.
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