目的:使用MDA-MB-231和HeLa细胞进行的基于四唑的细胞增殖试验显示,3,4-二氢-lacticin(3,4-DHL),一种从RoseaAL22中分离的化合物,具有抗癌特性。在3,4-DHL处理的细胞中观察到凋亡细胞死亡。Lactucopicrin,一个相关的化合物,据报道,对不同类型的癌症具有抗癌活性。然而,关于乳菌素抗癌机制的数据有限。本研究旨在研究3,4-DHL对MDA-MB-231细胞凋亡的诱导作用。
方法:形态变化,线粒体膜电位的变化,研究了用3,4-DHL处理的MDA-MB-231细胞的凋亡诱导。此外,分子对接和吸收,分布,新陈代谢,排泄,进行抗凋亡蛋白的毒性(ADMET)分析以确定3,4-DHL的效应机制。
结果:3,4-DHL在37.62μg/ml的半最大抑制浓度下诱导细胞毒性,以及凋亡和存活细胞的各种形态学改变。此外,3,4-DHL处理的细胞显示线粒体膜电位去极化,强烈的膜联蛋白V-异硫氰酸荧光素染色,并增加了caspase3和8的活性。分子对接研究表明,3,4-DHL应与各种抗凋亡蛋白的活性位点结合,形成稳定的复合物。
结论:我们的发现表明,3,4-DHL在癌症治疗中具有作为凋亡诱导剂的巨大潜力。然而,在评估3,4-DHL作为癌症化疗中的抗癌剂时,需要进一步的体内确认。
OBJECTIVE: Tetrazolium-based cell proliferation assays using MDA-MB-231 and HeLa cells revealed that 3,4-dihydro-lactucin (3,4-DHL), a compound isolated from Microbispora rosea AL22, possesses anticancer properties. Apoptotic cell death was observed in 3,4-DHL-treated cells. Lactucopicrin, a related compound, reportedly exerts anticancer activity against different cancer types. However, data on the anticancer mechanism of lactucins are limited. This study aimed to investigate apoptosis induction in MDA-MB-231 cells treated with 3,4-DHL.
METHODS: Morphological changes, changes in mitochondrial membrane potential, and apoptosis induction in MDA-MB-231 cells treated with 3,4-DHL were investigated. Furthermore, molecular docking and absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis of anti-apoptotic proteins were performed to determine the effector mechanism of 3,4-DHL.
RESULTS: 3,4-DHL induced cytotoxicity at a half-maximal inhibitory concentration of 37.62 μg/ml, along with various morphological alterations in apoptotic and viable cells. Furthermore, 3,4-DHL-treated cells showed mitochondrial membrane potential depolarization, intense annexin V-fluorescein isothiocyanate staining, and increased caspase 3 and 8 activities. Molecular-docking studies demonstrated that 3,4-DHL should bind to the active site of various anti-apoptotic proteins, forming stable complexes.
CONCLUSIONS: Our findings revealed that 3,4-DHL has great potential to be used as an apoptosis-inducing agent in cancer therapy. However, further in-vivo confirmation is required in evaluation of 3,4-DHL as an anticancer agent in cancer chemotherapy.