研究动态
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Cymbopogon proximus 植物化学物质通过 CDK2/细胞周期蛋白 A2 抑制诱导 A549 肺癌细胞系 S 期停滞:气相色谱-质谱法和分子对接分析。

Cymbopogon proximus phytochemicals induce S-phase arrest in A549 lung cancer cell lines via CDK2/cyclin A2 inhibition: gas chromatography-mass spectrometry and molecular docking analyses.

发表日期:2024 May 24
作者: Noha A Seif-Eldein, Salwa A Abu El Wafa, Esraa Z Mohammed, Abeer Temraz
来源: Bone & Joint Journal

摘要:

Cymbopogon proximus 包含几种据报道具有抗癌活性的植物成分;然而,缺乏对该植物抗癌潜力的研究。使用极性逐渐增加的溶剂提取 C. proximus。使用 MTT 测定法检查 C. proximus 提取物对肝 (HepG2)、肺 (A549)、前列腺 (PC3) 和骨 (MG63) 细胞系的体外细胞毒活性,并与阿霉素进行比较。使用流式细胞术分析细胞周期以识别抑制阶段。使用 GC/MS 技术检查最活跃级分的化学成分。采用分子对接探讨了A549的细胞毒作用机制,并通过Western blot分析证实了结果。石油醚馏分是对抗 A549 的高效馏分,IC50 = 14.02 ± 2.79。对 Pet.Eth 进行 GC/MS 分析,鉴定出不皂化物质中的 9 种化合物和皂化馏分中的 27 种成分。邻苯二甲酸二正辛酯、3-β-羟基-11.13(18)-二烯-30-油酸甲酯、榄香烯醇烃、亚油酸和亚油酸与 CDK2 相比表现出最低的对接结合分数和相似的结合模式这是通过天然配体 R-Roscovitine“CDK2 ATP 抑制剂”实现的。蛋白质印迹分析表明,Pet.Eth 组分在 A549 细胞系中抑制 CDK2/cyclinA2 蛋白表达。© 2024 Walter de Gruyter GmbH,柏林/波士顿。
Cymbopogon proximus comprises several phytoconstituent classes that are reported to possess anticancer activity; however, studies on the anticancer potentials of the plant are lacking. C. proximus was extracted using solvents with increasing polarity. In-vitro cytotoxic activity of C. proximus extracts was examined against liver (HepG2), lung (A549), prostate (PC3), and bone (MG63) cell lines using MTT assay in comparison to doxorubicin. Flow cytometry was used to analyze the cell cycle for identification of the phase of inhibition. Chemical composition of the most active fraction was examined using the GC/MS technique. Molecular docking was used to explore the mechanism of cytotoxicity against A549, and the results were confirmed by Western blot analysis. Petroleum ether fraction was the highly effective fraction against A549 with IC50 = 14.02 ± 2.79. GC/MS analysis of Pet.Eth led to the identification of nine compounds in unsaponifiable matter and 27 components in the saponifiable fraction. Di-N-octyl phthalate, 3-β-hydroxylean-11.13(18)-dien-30-oic acid methyl ester, elemol hydrocarbons, linoelaidic acid and linoleic acid demonstrated the lowest docking binding scores and similar binding modes against CDK2 as compared to that attained by the native ligand R-Roscovitine "CDK2 ATP inhibitor". Western blot analysis demonstrated that CDK2/cyclinA2 protein expression has been suppressed in A549 cell lines by Pet.Eth fraction.© 2024 Walter de Gruyter GmbH, Berlin/Boston.