Unraveling the Ferroptosis-inducing Potential of Methanol Leaves Extract of Prosopis Juliflora Via Downregulation of SLC7A11 and GPX4 mRNA Expression in A549 Lung Cancer Cells.

IF 3.5 4区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current medicinal chemistry Pub Date : 2024-10-24 DOI:10.2174/0109298673343133241011072425

Nawaf Alshammari, Pratibha Pandey, Alya Redhwan, Hadeel R Bakhsh, Sorabh Lakhanpal, Safia Obaidur Rab, Ajay Singh, Mohd Saeed, Fahad Khan, Mohd Asif Shah

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引用次数: 0

Abstract

Introduction: Prosopis juliflora has been employed in many traditional treatments. As evidenced by our earlier research, Prosopis juliflora leaf methanol extract (PJME) has a promising future in the fight against lung cancer. It may also be used in conjunction with other treatments to effectively manage lung cancer.

Aims and objective: The main objective of this study was to explore the potential of PJME to inhibit lung cancer in A549 cells, along with its underlying mechanisms of action.

Method: The antiproliferative effects were determined using MTT and LDH tests. Apoptosis- inducing capacity was evaluated using the DAPI staining, caspase-3 test, cytochrome C assay, PARP cleavage, and qRT-PCR. To investigate the mechanism of action of PJME in lung cancer, the levels of ROS, MMP, GSH, MDA, and specific ferroptosis indicators were measured.

Results: The experimental data of the current study indicated that exposure of A549 cells to PJME reduced cell viability and increased cellular cytotoxicity. The apoptosis-inducing ability of PJME in A549 cells was validated by enhanced nuclear condensation, level of the caspase- 3, cytochrome C, and PARP release. In addition, qRT-PCR investigations verified that the administration of PJME led to a decrease in the expression of anti-apoptotic gene Bcl2 while enhancing the mRNA level of pro-apoptotic genes, such as Bax and caspase-3, in A549 cells.

Conclusion: The study also found that PJME has the ability to activate ferroptosis pathways, as evidenced by elevated reactive oxygen species (ROS) generation, changes in the levels of antioxidant markers (MDA and GSH), and decreased expression of SLC7A11 and GPX4. The results of the present study clearly showed that PJME inhibited the proliferation of A549 cells and induced ferroptosis by reducing the expression of the important targets SLC7A11 and GPX4. Further research is necessary to fully understand the clinical efficacy of PJME before it can be investigated as supplemental or adjuvant therapy for lung cancer.

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通过下调 SLC7A11 和 GPX4 mRNA 在 A549 肺癌细胞中的表达，揭示前胡甲醇叶提取物的铁诱导潜能

介绍：许多传统疗法中都使用了崖柏。我们早前的研究表明，糙叶树叶甲醇提取物（PJME）在抗击肺癌方面具有广阔的前景。它还可与其他疗法结合使用，有效控制肺癌：本研究的主要目的是探索 PJME 抑制 A549 细胞肺癌的潜力及其作用机制：方法：使用 MTT 和 LDH 试验测定抗增殖作用。采用 DAPI 染色、caspase-3 检测、细胞色素 C 检测、PARP 裂解和 qRT-PCR 技术评估了 PJME 诱导细胞凋亡的能力。为了研究 PJME 在肺癌中的作用机制，还测定了 ROS、MMP、GSH、MDA 和特定铁变态反应指标的水平：本研究的实验数据表明，A549细胞暴露于PJME后，细胞活力降低，细胞毒性增强。PJME对A549细胞的凋亡诱导能力通过细胞核凝结、Caspase-3水平、细胞色素C和PARP释放的增强得到了验证。此外，qRT-PCR 研究还证实，服用 PJME 后，A549 细胞中抗凋亡基因 Bcl2 的表达量减少，而促凋亡基因（如 Bax 和 caspase-3）的 mRNA 水平升高：研究还发现，PJME 有能力激活铁凋亡途径，这体现在活性氧（ROS）生成的增加、抗氧化标志物（MDA 和 GSH）水平的变化以及 SLC7A11 和 GPX4 表达的减少。本研究的结果清楚地表明，PJME 通过降低重要靶标 SLC7A11 和 GPX4 的表达，抑制了 A549 细胞的增殖并诱导了铁变态反应。要充分了解PJME的临床疗效，还需要进一步的研究，才能将其作为肺癌的辅助或辅助治疗手段。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current medicinal chemistry 医学-生化与分子生物学

CiteScore

8.60

自引率

2.40%

发文量

468

审稿时长

3 months

期刊介绍： Aims & Scope Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews and guest edited thematic issues written by leaders in the field covering a range of the current topics in medicinal chemistry. The journal also publishes reviews on recent patents. Current 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.