Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH, U.S.A.
Departamento de Productos Naturales, Instituto de Química, Universidad Nacional Autónoma de México, Ciudad Universitaria, Mexico.
Anticancer Res. 2020 Dec;40(12):6637-6647. doi: 10.21873/anticanres.14688. Epub 2020 Dec 7.
BACKGROUND/AIM: This study aimed to uncover the effects of (+)-betulin on the NF-κB-apoptotic pathway in MDA-MB-231 cells, and determine its toxicity and protein expression in vivo.
Cell cytotoxicity and toxicity were determined using the SRB assay and a zebrafish model, respectively. Western blot, mitochondrial transmembrane potential (MTP), and computational modeling analysis were performed.
(+)-betulin inhibited the growth of MDA-MB-231 cells, but did not induce toxicity in zebrafish. (+)-Betulin inhibited the activity of NF-κB p65 in silico and in vitro. In cells, (+)-betulin down-regulated NF-κB p50 and 65, IKKα and β, ICAM-1 and bcl-2 expressions. Cell co-treatment with (+)-betulin and TNFα increased the (+)-betulin cytotoxic potential. Moreover, (+)-betulin induced the loss of MTP. Furthermore, (+)-betulin, in zebrafish, down-regulated the expression of NF-κB p65, IKKα, ΙΚΚβ and procaspase-3.
The results contribute to the understanding of the mode of action on apoptosis induction by inhibiting NF-κB pathway in MDA-MB-231 cells.
背景/目的：本研究旨在揭示（+）-白桦脂醇对 MDA-MB-231 细胞中 NF-κB-凋亡途径的影响，并确定其在体内的毒性和蛋白表达。
分别采用 SRB 测定法和斑马鱼模型测定细胞细胞毒性和毒性。进行 Western blot、线粒体跨膜电位（MTP）和计算建模分析。
（+）-白桦脂醇抑制 MDA-MB-231 细胞的生长，但在斑马鱼中不诱导毒性。（+）-白桦脂醇在计算机模拟和体外抑制 NF-κB p65 的活性。在细胞中，（+）-白桦脂醇下调 NF-κB p50 和 65、IKKα 和 β、ICAM-1 和 bcl-2 的表达。细胞与（+）-白桦脂醇和 TNFα 共同处理可增加（+）-白桦脂醇的细胞毒性潜力。此外，（+）-白桦脂醇诱导 MTP 丧失。此外，（+）-白桦脂醇在斑马鱼中下调 NF-κB p65、IKKα、IKKβ 和 procaspase-3 的表达。
这些结果有助于了解通过抑制 NF-κB 途径诱导 MDA-MB-231 细胞凋亡的作用模式。
