AccScience Publishing / ITPS / Volume 6 / Issue 2 / DOI: 10.36922/itps.0618
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ORIGINAL RESEARCH ARTICLE

Evaluation of genotoxicity of (4-fluorophenyl) thiazolidin-4-one in CHO-K1 cells

Jhansi Mamilla1† Kalpana Javvaji1,3† Kavya Lekha Sunkara1 Umesh B. Kosurkar2 Ravindra M. Kumbhare2,3* Sunil Misra1,3*
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1 Genetic Toxicology Lab, Applied Biology, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, India
2 Department of Fluoro-Agrochemicals, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, India
3 Academy of Scientific and Innovative Research, Ghaziabad, India
INNOSC Theranostics and Pharmacological Sciences 2023, 6(2), 0618 https://doi.org/10.36922/itps.0618
Submitted: 18 April 2023 | Accepted: 18 July 2023 | Published: 7 August 2023
© 2023 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
Abstract

4-thiazolidinones are five-membered heterocyclic ring compounds with diverse pharmacological impacts. In a previous study, we reported a series of newly synthesized derivatives of 4-thiazolidinones with different functional groups, which exhibited anticancer activity against ovarian (SKOV3) and cervical (HeLa) cancer cell lines. Among these derivatives, (4-fluorophenyl) thiazolidin-4-one (4-TH) demonstrated potent cytotoxic activity against SKOV3, with an IC50 value of 12.3 μM. However, it was also found to be extremely toxic to normal cells (CHO-K1) with an IC50 of 7.5 μM. Before considering its use in cancer research, it is crucial to gain a comprehensive understanding of its potential genotoxic effects on normal cells. In this study, we aimed to assess the in vitro cytogenetic toxicity of 4-TH using normal Chinese hamster ovary cells (CHO-K1). Referring to the IC50 of 4-TH, we selected three sub-lethal concentrations (2, 5, and 7.5 μM) and treated CHO-K1 cells for 24 h (one cell cycle duration) to estimate its dose-dependent induction of chromosome aberrations, and examine the effect of 4-TH on cell division, micronucleus induction potential and cell cycle arrest properties following standard protocols. The results showed that 4-TH was highly toxic to normal cells, as all three sublethal concentrations caused a statistically significant increase in the number of chromosomal aberrations (P < 0.001), formation of micronuclei (P < 0.01), and changes in the rate of cell division (mitotic index) (P < 0.05) compared to control. In addition, there was a significant increase in the number of cells in the G1 phase, indicating that all concentrations of 4-TH tested induced apoptosis. The evaluation of the cytotoxic, clastogenic, and aneugenic properties of 4-TH, a potent cytotoxic agent, will undoubtedly provide critical information for determining its safety and potential as an anticancer drug.

Keywords
Cytotoxicity
Chromosome aberration
Mitotic index
Micronucleus
Cell cycle
Funding
None.
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Conflict of interest
All the authors declare that they have no competing interests.
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INNOSC Theranostics and Pharmacological Sciences, Electronic ISSN: 2705-0823 Published by AccScience Publishing