白花大戟和前胡精油可抗细胞毒性筛选及其在肺癌和结肠癌细胞中的增强抗癌活性——载有生物相容性脂质纳米颗粒的研究。
Cytotoxic Screening and Enhanced Anticancer Activity of Lippia alba and Clinopodium nepeta Essential Oils-Loaded Biocompatible Lipid Nanoparticles against Lung and Colon Cancer Cells.
发表日期:2023 Jul 29
作者:
Boris Rodenak-Kladniew, María Agustina Castro, Rocío Celeste Gambaro, Juan Girotti, José Sebastián Cisneros, Sonia Viña, Gisel Padula, Rosana Crespo, Guillermo Raúl Castro, Stephan Gehring, Cecilia Yamil Chain, Germán Abel Islan
来源:
Cell Death & Disease
摘要:
植物和草药精油(EOs)具有广泛的药理作用,包括抗癌效果。本研究评估了白车前(化学型号莰烯醇,LaDEO)、白车前(化学型号环己酮,LaDEO)、毛川峨(CnEO)、桉树、鼠尾草、薄荷、野薄荷 和迷迭香对人类肺(A549)和结肠(HCT-116)癌细胞的细胞毒活性。细胞经0-500 µL/L浓度递增的EO处理24小时,并评估了细胞毒活性。LaDEO 和CnEO是最具活性的精油(IC50范围在145-275 µL/L之间)。采用气相色谱-质谱法测定了它们的成分。考虑到EO作为治疗药物的限制(溶解性差、挥发性和氧化),我们评估了LaDEO和CnEO包埋到固体脂质纳米粒子(SLN/EO)中是否增强了它们的抗癌活性。获得了高度稳定的球形SLN/LaDEO和SLN/CnEO SLN/EO,平均直径为140-150 nm,尺寸分散窄,Z电位约为-5 mV。精油的包埋显著增强了它们的抗癌活性,特别是暴露于SLN/CnEO(IC50为66 µL/L CnEO)的A549细胞。对SLN/CnEO的理化特性、生物安全性和抗癌机制也在A549细胞中进行了评估。SLN/CnEO含有97 ± 1% CnEO,在6个月的时间内非常稳定。观察到在酸性pH值(内溶酶体间隔)下,CnEO从SLN中释放。SLN/CnEO对血液成分具有良好的安全性,治疗浓度对正常WI-38细胞无毒。与游离CnEO相比,SLN/CnEO显著增强了A549细胞的细胞死亡和细胞迁移抑制。
Plant and herbal essential oils (EOs) offer a wide range of pharmacological actions that include anticancer effects. Here, we evaluated the cytotoxic activity of EO from Lippia alba (chemotype linalool), L. alba (chemotype dihydrocarvone, LaDEO), Clinopodium nepeta (L.) Kuntze (CnEO), Eucalyptus globulus, Origanum × paniculatum, Mentha × piperita, Mentha arvensis L., and Rosmarinus officinalis L. against human lung (A549) and colon (HCT-116) cancer cells. The cells were treated with increasing EO concentrations (0-500 µL/L) for 24 h, and cytotoxic activity was assessed. LaDEO and CnEO were the most potent EOs evaluated (IC50 range, 145-275 µL/L). The gas chromatography-mass spectrometry method was used to determine their composition. Considering EO limitations as therapeutic agents (poor water solubility, volatilization, and oxidation), we evaluated whether LaDEO and CnEO encapsulation into solid lipid nanoparticles (SLN/EO) enhanced their anticancer activity. Highly stable spherical SLN/LaDEO and SLN/CnEO SLN/EO were obtained, with a mean diameter of 140-150 nm, narrow size dispersion, and Z potential around -5mV. EO encapsulation strongly increased their anticancer activity, particularly in A549 cells exposed to SLN/CnEO (IC50 = 66 µL/L CnEO). The physicochemical characterization, biosafety, and anticancer mechanisms of SLN/CnEO were also evaluated in A549 cells. SLN/CnEO containing 97 ± 1% CnEO was highly stable for up to 6 months. An increased in vitro CnEO release from SLN at an acidic pH (endolysosomal compartment) was observed. SLN/CnEO proved to be safe against blood components and non-toxic for normal WI-38 cells at therapeutic concentrations. SLN/CnEO substantially enhanced A549 cell death and cell migration inhibition compared with free CnEO.