Journal of the Serbian Chemical Society 2022 Volume 87, Issue 9, Pages: 969-981
https://doi.org/10.2298/JSC210723035A
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Apoptosis induction in HeLa cervical cancer cell line by steroidal 16,17-seco-16,17a-dinitriles
Aleksić Lidija D. (Oncology Institute of Vojvodina, Faculty of Medicine, University of Novi Sad, Sremska Kamenica, Serbia)
Nikolić Andrea R. (University of Novi Sad, Faculty of Sciences, Department of Chemistry, Biochemistry and Environmental Protection, Novi Sad, Serbia)
Kojić Vesna V. 
(Oncology Institute of Vojvodina, Faculty of Medicine, University of Novi Sad, Sremska Kamenica, Serbia)
Sakač Marija N. (University of Novi Sad, Faculty of Sciences, Department of Chemistry, Biochemistry and Environmental Protection, Novi Sad, Serbia)
Jovanović-Šanta Suzana S. (University of Novi Sad, Faculty of Sciences, Department of Chemistry, Biochemistry and Environmental Protection, Novi Sad, Serbia), [email protected]
Steroids are good candidates for drug development, thanks to their low general toxicity and possibility for structure modifications connected with change of their activity. Several 16,17-secoandrost-4-ene-16,17a-dinitrile compounds were synthesized and screened for anticancer effect previously, including 6-oxo and 6-hydroxyimino compounds. This research is continued with the attempts for different synthetic strategy and evaluation of anticancer effect mechanism. Synthesis of 3-hydroxyimino compounds was successful, but inseparable mix of isomers was excluded from biological tests. Tested secodinitriles expressed cytotoxic effect on HeLa cervix cancer cells as a model system, with submicromolar to molar IC50 values, where 6-substituted derivatives were more effective. After 72 h treatment with equitoxic concentrations equal IC50 values of test compounds the mechanism of this effect was studied using flow cytometry and specific fluorescent dyes. Modest change in both G0/G1 and G2/M resting phases and change in mitochondrial membrane potential were noticed, while the most pronounced effect was apoptosis induction. Total apoptosis was in range 50.72–58.31 % in all cell samples treated with secodinitriles, compared to 7.44 % in control samples. Total percent of dead cells, including both apoptotic and necrotic, ranged from 55.24 to 65.34 %, compared to 10.68 % in control. Selectivity towards cancer cells is very important feature of these compounds indicating their potential use as lead compounds in the drug development for the treatment of cancers of steroid hormone-dependent tissues.
Keywords: secosteroids, anticancer effect, cell cycle, mitochondrial membrane potential, proapoptotic effect, flow cytometry
Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. 451-03-68/2022-14/200125
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