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通过大蒜鳞茎提取物探索ROS介导的人类三阴性乳腺癌抗癌潜力:治疗活性化合物的来源

Exploring the ROS-mediated anti-cancer potential in human triple-negative breast cancer by garlic bulb extract: A source of therapeutically active compounds.

作者信息

Upadhyay Shivbrat, Ahmad Rumana, Kumar Raushan, Ghildiyal Sneha, Singh Alok, Ahmad Khursheed, Husain Ishrat, Barkat Md Abul, Hassan Mohd Zaheen, Asiri Yahya I, Siddiqui Sahabjada

机构信息

Department of Biotechnology, Era's Lucknow Medical College and Hospital, Era University, Lucknow, 226003, India.

Department of Biochemistry, Era's Lucknow Medical College and Hospital, Era University, Lucknow, 226003, India.

出版信息

J Tradit Complement Med. 2024 Apr 11;14(6):644-655. doi: 10.1016/j.jtcme.2024.04.003. eCollection 2024 Nov.

Abstract

BACKGROUND AND AIM

L. has been used medicinally and traditionally since antiquity. This study sought to examine the ethanolic extract (ASEE) in inducing apoptosis in human triple-negative breast cancer (TNBC) MDA-MB-231 cells and the molecular interactions of the identified components with cell death markers using method.

EXPERIMENTAL PROCEDURE

Cytotoxicity of ASEE was tested on MCF-7, MDA-MB-231, and Normal Vero cells. The ROS production, apoptosis, MMP, and cell cycle study were conducted utilizing flow cytometer, and western blot was also performed for protein expression analysis. ASEE was phytochemially characterized by the HPLC while AutoDock Vina and iGEMDOCK tools investigated binding interactions.

RESULTS

The HPLC method identified two active organosulfur chemicals, allicin and alliin, in ASEE. MTT test revealed significant (p < 0.05) inhibition of breast cancer cells proliferation. The inhibitory effect of ASEE was more pronounced in MDA-MB-231 cells than in MCF-7 cells, however, no substantial cytotoxicity was seen in normal Vero cells. TNBC cells treated with high concentrations of ASEE were found in the late apoptotic stage and exhibited an increase in ROS level and a reduction in MMP. ASEE exposure increased the percentage of cells in the G2/M phase. ASEE upregulated the p53 and Bax proteins while downregulated the Bcl-2, p-Akt, and p-p38 proteins. Allicin and alliin compounds had strong binding affinity with targeted proteins of breast cancer, and both compounds also showed good pharmacokinetics and druglikeness properties.

CONCLUSION

ASEE could be useful in the treatment of human triple-negative breast cancer without any safety risks.

摘要

背景与目的

自古以来,大蒜就被用于医学和传统领域。本研究旨在研究大蒜乙醇提取物(ASEE)对人三阴性乳腺癌(TNBC)MDA-MB-231细胞凋亡的诱导作用,以及使用相关方法鉴定的成分与细胞死亡标志物的分子相互作用。

实验步骤

在MCF-7、MDA-MB-231和正常Vero细胞上测试ASEE的细胞毒性。利用流式细胞仪进行活性氧生成、凋亡、线粒体膜电位(MMP)和细胞周期研究,并进行蛋白质印迹分析蛋白表达。通过高效液相色谱法对ASEE进行植物化学表征,同时使用AutoDock Vina和iGEMDOCK工具研究结合相互作用。

结果

高效液相色谱法在ASEE中鉴定出两种活性有机硫化合物,大蒜素和蒜氨酸。MTT试验显示对乳腺癌细胞增殖有显著(p < 0.05)抑制作用。ASEE对MDA-MB-231细胞的抑制作用比MCF-7细胞更明显,然而,在正常Vero细胞中未观察到明显的细胞毒性。用高浓度ASEE处理的TNBC细胞处于晚期凋亡阶段,活性氧水平升高,线粒体膜电位降低。ASEE暴露增加了G2/M期细胞的百分比。ASEE上调p53和Bax蛋白,同时下调Bcl-2、p-Akt和p-p38蛋白。大蒜素和蒜氨酸化合物与乳腺癌靶向蛋白具有很强的结合亲和力,并且两种化合物还显示出良好的药代动力学和类药性质。

结论

ASEE可用于治疗人类三阴性乳腺癌,且无任何安全风险。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20a1/11752123/ea6f7c1153f6/ga1.jpg

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