The In Vitro Effect of Kynurenine Metabolites on Cell morphology, Cell cycle progression and the Induction of Apoptosis in Tumour Endothelioma Cells

Background: Cancer is one of the leading causes of death worldwide. The development of anticancer therapies plays a crucial role in mitigating tumour progression and metastasis. Kynurenine metabolites which include L-kynurenine, 3-hydroxykynurenine, 3-hydroxyanthranilic acid and quinolinic acid have been shown to inhibit T-cell proliferation resulting in a decrease in cell growth of natural killer (NK) cells and T cells. Research showed that L-kynurenine inhibits proliferation of melanoma cells in vitro. Methods: The present study aimed to explore the in vitro influence of L-kynurenine, quinolinic acid and kynurenic acid on endothelioma sEnd-2 cells at concentration ranges of 1 mM – 4 mM for 24 h, 48 h and 72 h on cell morphology, cell cycle progression and induction of apoptosis. Results and Discussion: The half inhibitory concentration (IC50), as determined using GraphPad Prism, for L-kynurenine, quinolinic acid and kynurenic acid was 10.77 mM, 14.78 mM and 535.40 mM respectively. Optical transmitted light differential interference contrast and hematoxylin and eosin staining revealed the presence of cells blocked in metaphase, formation of apoptotic bodies and compromised cell density in L-kynurenine- and quinolinic acid- treated cells. A statistically significant increase in the number of cells present in the sub-G1 phase was observed in L-kynurenine-treated samples. Conclusion: It can be concluded that L-kynurenine exerts an antiproliferative effect on the sEnd-2 cell line by a decrease in cell growth and proliferation and metaphase block. These hallmarks suggest cell death via apoptosis. Further research will be conducted on L-kynurenine to assess the effect on cell adhesion in vitro and in vivo. This research was supported by the following grants: The Research Development Programme at the University of Pretoria awarded to Dr YN Hlophe; National Research Foundation awarded to Dr YN Hlophe (A1F4685 & N1F580); The University Capacity Development Programme (UCDP) awarded to Ms Tatchum (A1D783 & N1F120). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.