Identification of a novel anticancer compound through screening of a drug library on multicellular spheroids | ||||
| Egyptian Pharmaceutical Journal | ||||
| Volume 18, Issue 3, July 2019, Page 188-200 PDF (1.13 MB) | ||||
| DOI: 10.4103/epj.epj_16_19 | ||||
 View on SCiNiTO | ||||
| Author | ||||
Walid Fayad
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| Abstract | ||||
| Background and objectives A multicellular cancer spheroid model has proven to mimic the in-vivo tumors more closely compared with the conventionally used monolayer model. Thus, the spheroid model estimates the in-vivo activity more accurately than its counterpart the monolayer model. Accordingly, a library of 320 chemically diverse compounds was screened for their cytotoxicity against MCF7 human breast carcinoma spheroids, aiming for identification of novel compounds active against this type of solid tumor. Materials and methods MCF7 spheroids were generated in 96-well plates by a centrifugation method. The spheroids took 5 days to reach ∼500-μm diameter and were ready for treatment. The initial screen was performed at 50 μM in triplicates. A dose–response study followed the initial screen. A counterscreen was carried out using RPE1 normal cell spheroids to identify the selectivity of active compounds. The acid phosphatase method was applied to measure the cytotoxicity of compounds. A clonogenic assay was used to investigate the viability of remaining cells after treatment with test compounds. Results and conclusion The compound (4,5-dibromo-6-oxo-1(6H)-pyridazinyl)methyl 3-chlorophenylcarbamate was identified in this study for the first time with reasonable toxicity on MCF7 cancer spheroids. This compound is suggested as a lead compound for the development of more active derivatives against solid tumors. Additionally, the multicellular spheroid model was proved as a useful and applicable platform for identification of novel compounds for the treatment of solid tumors. | ||||
| Keywords | ||||
| Breast carcinoma; Cancer; MCF7; RPE1; screening and anticancer drug discovery; spheroids; therapeutic window | ||||
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