Four newly synthesized enones induce mitochondrial-mediated apoptosis and G2/M cell cycle arrest in colorectal and cervical cancer cells.

Autor:	Bulić M; University Clinical Centre of Serbia, Centre of Medical Biochemistry Pasterova 2 Belgrade 11000 Serbia m.bulic81@yahoo.com., Nikolić I; Department of Biochemistry, University of Kragujevac, Faculty of Medical Sciences Svetozara Markovića 69 Kragujevac 34000 Serbia marijabcd@gmail.com angelkg2009@gmail.com mitrovicmarina34@gmail.com +381 65 84 777 68.; Centre for Research on Harmful Effects of Biological and Chemical Hazards Kragujevac Serbia., Mitrović M; Department of Biochemistry, University of Kragujevac, Faculty of Medical Sciences Svetozara Markovića 69 Kragujevac 34000 Serbia marijabcd@gmail.com angelkg2009@gmail.com mitrovicmarina34@gmail.com +381 65 84 777 68.; Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac Svetozara Markovica 69 Kragujevac 34000 Serbia., Muškinja J; Department of Science, University of Kragujevac, Institute for Information Technologies Jovana Cvijica bb Kragujevac 34000 Serbia jovana.muskinja@gmail.com tamaratasha34@gmail.com., Todorović T; Department of Science, University of Kragujevac, Institute for Information Technologies Jovana Cvijica bb Kragujevac 34000 Serbia jovana.muskinja@gmail.com tamaratasha34@gmail.com., Anđelković M; Department of Biochemistry, University of Kragujevac, Faculty of Medical Sciences Svetozara Markovića 69 Kragujevac 34000 Serbia marijabcd@gmail.com angelkg2009@gmail.com mitrovicmarina34@gmail.com +381 65 84 777 68.; Centre for Research on Harmful Effects of Biological and Chemical Hazards Kragujevac Serbia.
Jazyk:	angličtina
Zdroj:	RSC advances [RSC Adv] 2024 Oct 25; Vol. 14 (46), pp. 33987-34004. Date of Electronic Publication: 2024 Oct 25 (Print Publication: 2024).
DOI:	10.1039/d4ra06529h
Abstrakt:	Over the last few decades, we have gained insight into how researchers attempted to modify some natural molecules to be utilized as prospective agents for cancer treatment. Many scientists synthesized new natural compounds by incorporating specific functional groups and metals that improved their antitumor activity while reducing undesirable side effects. In this investigation, we synthesized four novel structurally modified enones that differ in the functional groups attached to the carbonyl group of the enone system (methyl - E1; isopropyl - E2; isobutyl - E3; and cyclopropyl - E4) and explored their anticancer potential against human carcinoma of the colon HCT-116, the cervical HeLa, and normal lung cells MRC-5. From the findings, all the newly synthesized enones exhibited potent cytotoxic activity against the cancer cells while normal cells remained unharmed, with varying potencies among the various enones. We employed the MTT assay to assess enones's (E1-E4) cytotoxic effects, IC50 values and selectivity index in tumor cells. Furthermore, the newly synthesized enones induced cell death in cancer cells through apoptosis by promoting changes in cellular morphology, activating apoptotic regulators Bax and caspase 3, and inhibiting Bcl-2. The enones induced changes in the mitochondrial membrane potential, a release of cytochrome c, and a cell cycle arrest at the G2/M phase, thus inhibiting the growth of cancer cells. In conclusion, we demonstrated the anticancer potential of newly synthesized enones as promising candidates for future cancer treatments, especially for colon cancer, due to their selective cytotoxicity against these cancer cells. Further, in vivo studies are warranted to explore their full therapeutic potential. Competing Interests: There are no conflicts to declare. (This journal is © The Royal Society of Chemistry.)
Databáze:	MEDLINE
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