Fikry Eman, Orfali Raha, Perveen Shagufta, Ghaffar Safina, El-Shafae Azza M, El-Domiaty Maher M, Tawfeek Nora
Department of Pharmacognosy, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt.
Department of Pharmacognosy, Collage of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
Pharmaceuticals (Basel). 2025 May 22;18(6):771. doi: 10.3390/ph18060771.
This study investigates the phytochemical composition and anticancer activity of leaf essential oil (MQLEO) from Egypt. Chemical profiling was performed using GC/MS. Anticancer activity was assessed through cytotoxicity screening against multiple cancer cell lines, with a subsequent evaluation of cell migration, apoptosis, and cell cycle analysis on the most sensitive line (A549). Network pharmacology and molecular docking analyses were employed to identify potential molecular targets and pathways. GC/MS analysis revealed a unique profile dominated by 1,8-cineole (31.57%), α-pinene isomers (both 1R and 1S forms, collectively 21.26%), and sesquiterpene alcohols (viridiflorol: 13.65%; ledol: 4.55%). These results diverge from prior studies, showing a 25.63% decrease in 1,8-cineole and no detectable α-terpineol, suggesting environmental, genetic, or methodological impacts on biosynthesis. In vitro tests revealed selective cytotoxicity against A549 lung cancer cells (IC = 18.09 μg/mL; selectivity index = 4.30), meeting NCI criteria. Staurosporine was used as a positive control to validate the assays, confirming the reliability of the methods. MQLEO also inhibited cell migration (62-68% wound closure reduction) and induced apoptosis (24.32% vs. 0.7% in controls). Cell cycle arrest at the G-G phase implicated cyclin-dependent kinase regulation. Network pharmacology identified ESR1, CASP3, PPARG, and PTGS2 as key targets, with MQLEO components engaging apoptosis, inflammation (TNF, IL-17), and estrogen pathways. MQLEO demonstrates promising anticancer activity through multiple mechanisms including apoptosis induction, cell cycle arrest, and migration inhibition. The multi-target activity profile highlights its potential as a therapeutic candidate for lung cancer, warranting further in vivo validation and pharmacokinetic studies to advance clinical translation.
本研究调查了来自埃及的叶精油（MQLEO）的植物化学成分和抗癌活性。使用气相色谱/质谱联用仪（GC/MS）进行化学分析。通过对多种癌细胞系的细胞毒性筛选评估抗癌活性，随后对最敏感的细胞系（A549）进行细胞迁移、凋亡和细胞周期分析。采用网络药理学和分子对接分析来确定潜在的分子靶点和途径。GC/MS分析显示了一个独特的图谱，主要成分包括1,8-桉叶素（31.57%）、α-蒎烯异构体（1R和1S两种形式，总计21.26%）和倍半萜醇（绿花白千层醇：13.65%；喇叭茶醇：4.55%）。这些结果与先前的研究不同，显示1,8-桉叶素减少了25.63%，且未检测到α-松油醇，表明环境、遗传或方法学对生物合成有影响。体外试验显示对A549肺癌细胞具有选择性细胞毒性（IC = 18.09 μg/mL；选择性指数 = 4.30），符合美国国立癌症研究所（NCI）标准。使用星形孢菌素作为阳性对照来验证试验，证实了方法的可靠性。MQLEO还抑制细胞迁移（伤口闭合减少62 - 68%）并诱导凋亡（24.32%，而对照组为0.7%）。细胞周期停滞在G - G期涉及细胞周期蛋白依赖性激酶调节。网络药理学确定雌激素受体1（ESR1）、半胱天冬酶3（CASP3）、过氧化物酶体增殖物激活受体γ（PPARG）和环氧合酶2（PTGS2）为关键靶点，MQLEO的成分参与凋亡、炎症（肿瘤坏死因子、白细胞介素-17）和雌激素途径。MQLEO通过多种机制展现出有前景 的抗癌活性，包括诱导凋亡、细胞周期停滞和迁移抑制。多靶点活性图谱突出了其作为肺癌治疗候选药物的潜力，需要进一步进行体内验证和药代动力学研究以推进临床转化。
