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Abstract The current study examined the anticancer potential of 80 synthetic organic compounds at 50µM using in vitro two-dimensional (2D) and three-dimensional (3D) spheroids model breast adenocarcinoma (MCF7) models. The most promising six cytotoxic compounds on the 3D spheroids model (> 70% growth cytotoxicity) were counter-screened for their safety on normal cells (RPE1 cell line) grown as 3D spheroids. In parallel, the six compounds were tested for their pro-apoptotic activity using the M30 Cyto death ELISA assay. Based on the activity on MCF7 3D spheroids model, half maximum inhibitory concentration (IC 50 fourfold increase of negative control), three compounds were considered the most promising and were selected for further investigation, named: F03, F06 and C02. These three candidates underwent further gene expression profiling of apoptosis and inflammatory related genes by quantitative real-time polymerase chain reaction (qRT-PCR). The gene expression results for the three compounds indicated favorable pro-apoptotic activity while unfavorable pro-inflammatory induction. Statistical analysis of the Xlog P values of the 3D spheroids model hits compared to that of the 80-compounds library showed a significant tendency for higher XlogP values in the 3D spheroids model hits sub-group, most probably due to the higher penetrability of lipophilic compounds into the tumor mass. The presented work can be considered a pilot model for an approach in anticancer drug discovery.
Mahmoud et al. (Wed,) studied this question.