3D HeLa spheroids as a model for investigating the anticancer activity of Biginelli-hybrids. (25th August 2021)

• Record Type: Journal Article
• Authors: Crnogorac, Marija Đorđić; Matić, Ivana Z.; Damjanović, Ana; Janković, Nenad; Krivokuća, Ana; Stanojković, Tatjana
• Is Part Of: Chemico-biological interactions. Volume 345(2021)
• Publication Date: 2021-08-25
• Subjects: Biginelli-hybrids -- HeLa 3D spheroids -- Anticancer activity -- Invasiveness -- Cytotoxicity; Biochemistry -- Periodicals; Toxicological chemistry -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biochimie -- Périodiques; Toxicologie biochimique -- Périodiques; 572
• DOI: 10.1016/j.cbi.2021.109565
• Languages: English
• ISSNs: 0009-2797

Abstract

Abstract: In previous study, we examined the anticancer effects of novel Biginelli-hybrids against HeLa cell line on 2D monolayer culture. The five most effective compounds were chosen for further analysis of their anticancer activity against HeLa spheroids. Using the 3D models implies the possible differences in anticancer effects and mechanisms of activity of tested compounds. The compounds 4c and 4 d exerted the strongest activity against 3D HeLa spheroids and induced to some extent loosened cell-cell contacts in spheroids, leading to the largest reduction in the diameter of the spheroids. Additionally, the highest accumulation of the cells in the subG1 phase of the cell cycle was observed after the treatment with compounds 4d and 4c, while the compound 4f led to the G2/M arrest. The invasion potential of treated HeLa cells in spheroids was monitored by imaging of spheroids embedded in a matrix made of matrigel and collagen and by determination of MMP2, MMP9, and VEGF gene expression levels. The compound 4l did not show invasion-suppressive activity, while the compounds 4c and 4d exerted the strongest anti-invasive activity. Highlights: 3D culture models are of crucial importance in anticancer drug discovery. Novel Biginelli-hybrids showed significant anticancer potential. Two mechanisms of anticancer activity were detected, apoptosis and G2/M arresting. Differences in Bignelli-hybrids activities - attributed to hydrophobic properties.