Novel thalidomide analogs: Anti-angiogenic and apoptotic effects on Hep-G2 and MCF-7 cancer cell lines

Thalidomide is one of the anti-angiogenic drugs, which have been investigated as a possible treatment for various cancers and diseases. This work aimed to study novel thalidomide analogs for their anti-cytotoxicity, anti-angiogenic, treratogenic gene (FGF-2) expression as well as changes in histone deacetylase (HDAC) activity and nuclear factor kappa-B (NF-κB) level using two different cancer cell lines (Hep-G2 and MCF-7 cells). MTT assay was used to assess the cytotoxic effect of thalidomide analogs against Hep-G2 and MCF-7 cells. HDAC activity was estimated by colorimetric assay. NFκB- P65, pro-angiogenesis and anti-angiogenesis markers were determined by Enzyme-linked immunosorbent assay (ELISA). FGF-2 expression was confirmed by reverse transcription-polymerase chain reaction (RT-PCR). Thalidomide dithiocarbamate analogs 1, 5 and thalidomide dithioate analog 3 showed elevation in their cytotoxic activity better than thalidomide. Thalidomide dithioate analog 2 and thalidomide dithiocarbamate analog 4 showed reduction in pro-angiogenic and elevation of anti-angiogenic factors in both cell lines; furthermore, analog 1 is the most potent analog in MCF-7 cells as an anti-angiogenic agent. In Hep-G2 cells, analogs 1, 2, 4 showed a significant increase while analogs 3 and 5 induced a significant decrease in NF-κB level in relation to thalidomide. A drastic decline in HDAC activity was demonstrated in the following order 2 > thalidomide > 1 > 3 > 5 > 4 of the control activity. In conclusion, this study showed that thalidomide analogs are more potent anti-tumor agents with more pronounced effect by working selectively on specific types of tumors than thalidomide. © 2014 Elsevier Masson SAS.