Kojic Acid Derivative as an Antimitotic Agent That Selectively Kills Tumour Cells
<b>Background/Objectives:</b> The primary method used to pharmacologically arrest cancer development and its metastasis is to disrupt the cell division process. There are a few approaches that may be used to meet this objective, mainly through inhibiting DNA replication or mitosis. Despi...
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2024-12-01
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| author | Giuseppina Pichiri Marco Piludu Terenzio Congiu Nicole Grandi Pierpaolo Coni Monica Piras Mariusz Jaremko Joanna Izabela Lachowicz |
| author_facet | Giuseppina Pichiri Marco Piludu Terenzio Congiu Nicole Grandi Pierpaolo Coni Monica Piras Mariusz Jaremko Joanna Izabela Lachowicz |
| author_sort | Giuseppina Pichiri |
| collection | DOAJ |
| description | <b>Background/Objectives:</b> The primary method used to pharmacologically arrest cancer development and its metastasis is to disrupt the cell division process. There are a few approaches that may be used to meet this objective, mainly through inhibiting DNA replication or mitosis. Despite intensive studies on new chemotherapeutics, the biggest problem remains the side effects associated with the inhibition of cell division in non-tumoural host cells. <b>Methods:</b> The efficacy and selectivity of the kojic acid derivative (L1) was studied in vitro with the use of tumoural (Caco2, SW480, HT29, T98G) and non- tumoural (HEK293T, RAW) cell lines. Light and electron microscopy observations were supported by the next generation sequencing (NGS), cytoflow, and spectroscopy analysis of mRNA and biomolecules, respectively. <b>Results:</b> The light and electron microscopy observations showed that L1 treatment leads to significant morphological changes in Caco2 cells, which are characteristic of mitosis arrest. Moreover, the fluorescent tubulin staining revealed the formation of tubulin ring structure associated with the apoptotic stage. Mitotic exit into apoptosis was further conformed by the cytoflow of early/late apoptosis stages and caspase-3 analysis. NGS investigation showed differentiated expressions of genes involved in mitosis and apoptosis processes. The observed IC50 in tumoural cell lines were as follows: Caco2 (IC50 = 68.2 mM), SW480 (IC50 = 15.5 mM), and HT29 (IC50 = 4.7 mM). <b>Conclusions:</b> The findings presented here suggest that L1 could be a valid candidate for oral prevention and/or chemotherapy in colorectal cancer. Considering high selectivity of L1 versus tumoural cell lines, more in-depth mechanistic studies could reveal unknown stages in carcinogenesis. |
| format | Article |
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| institution | Kabale University |
| issn | 1424-8247 |
| language | English |
| publishDate | 2024-12-01 |
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| series | Pharmaceuticals |
| spelling | doaj-art-4801f554844b46528549e5182a2ed9a12025-01-24T13:44:59ZengMDPI AGPharmaceuticals1424-82472024-12-011811110.3390/ph18010011Kojic Acid Derivative as an Antimitotic Agent That Selectively Kills Tumour CellsGiuseppina Pichiri0Marco Piludu1Terenzio Congiu2Nicole Grandi3Pierpaolo Coni4Monica Piras5Mariusz Jaremko6Joanna Izabela Lachowicz7Department of Medical Sciences and Public Health, University of Cagliari, Cittadella Universitaria, 09042 Monserrato, ItalyDepartment of Biomedical Sciences, University of Cagliari, Cittadella Universitaria, 09042 Monserrato, ItalyDepartment of Medical Sciences and Public Health, University of Cagliari, Cittadella Universitaria, 09042 Monserrato, ItalyDepartment of Life and Environmental Sciences, University of Cagliari, Cittadella Universitaria, 09042 Monserrato, ItalyDepartment of Medical Sciences and Public Health, University of Cagliari, Cittadella Universitaria, 09042 Monserrato, ItalyDepartment of Medical Sciences and Public Health, University of Cagliari, Cittadella Universitaria, 09042 Monserrato, ItalySmart-Health Initiative (SHI) and Red Sea Research Center (RSRC), Division of Biological and Environmental Sciences and Engineering (BESE), King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi ArabiaDepartment of Medical Sciences and Public Health, University of Cagliari, Cittadella Universitaria, 09042 Monserrato, Italy<b>Background/Objectives:</b> The primary method used to pharmacologically arrest cancer development and its metastasis is to disrupt the cell division process. There are a few approaches that may be used to meet this objective, mainly through inhibiting DNA replication or mitosis. Despite intensive studies on new chemotherapeutics, the biggest problem remains the side effects associated with the inhibition of cell division in non-tumoural host cells. <b>Methods:</b> The efficacy and selectivity of the kojic acid derivative (L1) was studied in vitro with the use of tumoural (Caco2, SW480, HT29, T98G) and non- tumoural (HEK293T, RAW) cell lines. Light and electron microscopy observations were supported by the next generation sequencing (NGS), cytoflow, and spectroscopy analysis of mRNA and biomolecules, respectively. <b>Results:</b> The light and electron microscopy observations showed that L1 treatment leads to significant morphological changes in Caco2 cells, which are characteristic of mitosis arrest. Moreover, the fluorescent tubulin staining revealed the formation of tubulin ring structure associated with the apoptotic stage. Mitotic exit into apoptosis was further conformed by the cytoflow of early/late apoptosis stages and caspase-3 analysis. NGS investigation showed differentiated expressions of genes involved in mitosis and apoptosis processes. The observed IC50 in tumoural cell lines were as follows: Caco2 (IC50 = 68.2 mM), SW480 (IC50 = 15.5 mM), and HT29 (IC50 = 4.7 mM). <b>Conclusions:</b> The findings presented here suggest that L1 could be a valid candidate for oral prevention and/or chemotherapy in colorectal cancer. Considering high selectivity of L1 versus tumoural cell lines, more in-depth mechanistic studies could reveal unknown stages in carcinogenesis.https://www.mdpi.com/1424-8247/18/1/11mitosisantimitotic agentsmicroscopynext generation sequencing (NGS)cytoflowapoptosis |
| spellingShingle | Giuseppina Pichiri Marco Piludu Terenzio Congiu Nicole Grandi Pierpaolo Coni Monica Piras Mariusz Jaremko Joanna Izabela Lachowicz Kojic Acid Derivative as an Antimitotic Agent That Selectively Kills Tumour Cells Pharmaceuticals mitosis antimitotic agents microscopy next generation sequencing (NGS) cytoflow apoptosis |
| title | Kojic Acid Derivative as an Antimitotic Agent That Selectively Kills Tumour Cells |
| title_full | Kojic Acid Derivative as an Antimitotic Agent That Selectively Kills Tumour Cells |
| title_fullStr | Kojic Acid Derivative as an Antimitotic Agent That Selectively Kills Tumour Cells |
| title_full_unstemmed | Kojic Acid Derivative as an Antimitotic Agent That Selectively Kills Tumour Cells |
| title_short | Kojic Acid Derivative as an Antimitotic Agent That Selectively Kills Tumour Cells |
| title_sort | kojic acid derivative as an antimitotic agent that selectively kills tumour cells |
| topic | mitosis antimitotic agents microscopy next generation sequencing (NGS) cytoflow apoptosis |
| url | https://www.mdpi.com/1424-8247/18/1/11 |
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