5-(carbamoylmethylene)-oxazolidin-2-ones as a promising class of heterocycles inducing apoptosis triggered by increased ROS levels and mitochondrial dysfunction in breast and cervical cancer

Armentano, B; Curcio, R; Brindisi, M; Mancuso, R; Rago, V; Ziccarelli, I; Frattaruolo, L; Fiorillo, M; Dolce, V; Gabriele, B; Cappello, AR

Abstract

Oxazolidinones are antibiotics that inhibit protein synthesis by binding the 50S ribosomal subunit. Recently, numerous worldwide researches focused on their properties and possible involvement in cancer therapy have been conducted. Here, we evaluated in vitro the antiproliferative activity of some 5-(carbamoylmethylene)-oxazolidin-2-ones on MCF-7 and HeLa cells. The tested compounds displayed a wide range of cytotoxicity on these cancer cell lines, measured by MTT assay, exhibiting no cytotoxicity on non-tumorigenic MCF-10A cells. Among the nine tested derivatives, four displayed a good anticancer potential. Remarkably, OI compound showed IC50 values of 17.66 and 31.10 µM for MCF-7 and HeLa cancer cells, respectively. Furthermore, we assessed OI effect on the cell cycle by FACS analysis, highlighting a G1 phase arrest after 72 h, supported by a low expression level of Cyclin D1 protein. Moreover, mitochondrial membrane potential was reduced after OI treatment driven by high levels of ROS. These findings demonstrate that OI treatment can inhibit MCF-7 and HeLa cell proliferation and induce apoptosis by caspase-9 activation and cytochrome c release in the cytosol. Hence, 5-(carbamoylmethylene)-oxazolidin-2-ones have a promising anticancer activity, in particular, OI derivative could represent a good candidate for in vivo further studies and potential clinical use.

Citation

Armentano, B., Curcio, R., Brindisi, M., Mancuso, R., Rago, V., Ziccarelli, I., …Cappello, A. (2020). 5-(carbamoylmethylene)-oxazolidin-2-ones as a promising class of heterocycles inducing apoptosis triggered by increased ROS levels and mitochondrial dysfunction in breast and cervical cancer. Biomedicines, 8(2), e35. https://doi.org/10.3390/biomedicines8020035

• Journal Article Type: Article
• Acceptance Date: Feb 16, 2020
• Publication Date: Feb 18, 2020
• Deposit Date: Feb 20, 2020
• Publicly Available Date: Feb 20, 2020
• Journal: Biomedicines
• Publisher: MDPI
• Volume: 8
• Issue: 2
• Pages: e35
• DOI: https://doi.org/10.3390/biomedicines8020035
• Keywords: oxazolidinones, apoptosis, mitochondria, ROS, anticancer compounds
• Publisher URL: https://doi.org/10.3390/biomedicines8020035
• Related Public URLs: https://www.mdpi.com/journal/biomedicines
• Additional Information: Additional Information : ** From MDPI via Jisc Publications Router ** Licence for this article: https://creativecommons.org/licenses/by/4.0/ **Journal IDs: eissn 2227-9059 **History: published 18-02-2020; accepted 16-02-2020