J. Mamilla, Kalpana Javvaji, Kavya Lekha Sunkara, U. Kosurkar, R. Kumbhare, S. Misra
{"title":"(4-氟苯基)噻唑烷-4- 1对CHO-K1细胞的遗传毒性评价","authors":"J. Mamilla, Kalpana Javvaji, Kavya Lekha Sunkara, U. Kosurkar, R. Kumbhare, S. Misra","doi":"10.36922/itps.0618","DOIUrl":null,"url":null,"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.","PeriodicalId":13673,"journal":{"name":"INNOSC Theranostics and Pharmacological Sciences","volume":"3 1","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2023-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Evaluation of genotoxicity of (4-fluorophenyl) thiazolidin-4-one in CHO-K1 cells\",\"authors\":\"J. Mamilla, Kalpana Javvaji, Kavya Lekha Sunkara, U. Kosurkar, R. Kumbhare, S. Misra\",\"doi\":\"10.36922/itps.0618\",\"DOIUrl\":null,\"url\":null,\"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.\",\"PeriodicalId\":13673,\"journal\":{\"name\":\"INNOSC Theranostics and Pharmacological Sciences\",\"volume\":\"3 1\",\"pages\":\"\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2023-08-07\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"INNOSC Theranostics and Pharmacological Sciences\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.36922/itps.0618\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"INNOSC Theranostics and Pharmacological Sciences","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.36922/itps.0618","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Evaluation of genotoxicity of (4-fluorophenyl) thiazolidin-4-one in CHO-K1 cells
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.