Department of Chemical Engineering, University of Salamanca, 37008 Salamanca, Spain.
Molecules. 2022 Apr 24;27(9):2735. doi: 10.3390/molecules27092735.
Isoprenoids are natural compounds essential for a great number of cellular functions. One of them is farnesol (FOH), which can reduce cell proliferation, but its low solubility in aqueous solvents limits its possible clinical use as a pharmacological tool. One alternative is the use of cyclodextrins (CDs) which house hydrophobic molecules forming inclusion complexes. To assess FOH potential application in anticancer treatments, Sulfobutylated β-cyclodextrin Sodium Salt (SBE-β-CD) was selected, due to it has high solubility, approbation by the FDA, and numerous studies that ensure its safety to be administered parenterally or orally without nephrotoxicity associated. The therapeutic action of farnesol and complex were studied in different carcinoma cells, compared with a normal cell line. Farnesol showed selectivity, affecting the viability of colon and liver cancer cells more than in breast cancer cells and fibroblasts. All cells suffered apoptosis after being treated with 150 μM of free FOH, but the complex reduced their cell viability between 50 and 75%. Similar results were obtained for both types of isomers, and the addition of phosphatidylcholine reverses this effect. Finally, cell cycle analysis corroborates the action of FOH as inducer of a G0/G1 phase; when the cells were treated using the complex form, this viability was reduced, reaching 50% in the case of colon and liver, 60% in fibroblasts, and only 75% in breast cancer.
异戊二烯类化合物是许多细胞功能所必需的天然化合物。其中之一是法呢醇（FOH），它可以减少细胞增殖，但由于其在水溶剂中的溶解度低，限制了其作为药理学工具的可能临床应用。一种替代方法是使用环糊精（CDs），它可以容纳形成包合复合物的疏水分子。为了评估 FOH 在癌症治疗中的潜在应用，选择了磺丁基-β-环糊精钠盐（SBE-β-CD），因为它具有高溶解度、FDA 批准以及大量研究确保其安全性，可通过肠内或口服给予而不会产生与肾毒性相关的副作用。法呢醇及其复合物的治疗作用在不同的癌细胞中进行了研究，并与正常细胞系进行了比较。法呢醇表现出选择性，对结肠癌和肝癌细胞的活力影响大于乳腺癌细胞和成纤维细胞。在用 150μM 的游离 FOH 处理后，所有细胞都发生了凋亡，但复合物将其细胞活力降低了 50%至 75%。两种类型的异构体都得到了类似的结果，添加磷脂酰胆碱会逆转这种效果。最后，细胞周期分析证实了 FOH 作为 G0/G1 期诱导剂的作用；当使用复合物形式处理细胞时，这种活力降低，在结肠癌和肝癌中降低到 50%，在成纤维细胞中降低到 60%，在乳腺癌中仅降低到 75%。
