An in vitro investigation of l-kynurenine, quinolinic acid, and kynurenic acid on B16 F10 melanoma cell cytotoxicity and morphology

Cell Biochem Funct. 2023 Oct;41(7):912-922. doi: 10.1002/cbf.3843. Epub 2023 Sep 3.

Abstract

The metastatic behavior of melanoma has accentuated the need for specific therapy targets. Compounds, namely l-kynurenine ( l-kyn), quinolinic acid (Quin), and kynurenic acid (KA) previously displayed antiproliferative and cytotoxic effects in vitro against cancer cells. Despite the growing interest in these compounds there are limited studies examining the in vitro effects on melanoma. In B16 F10 melanoma cells, RAW 264.7 macrophage cells, and HaCat keratinocyte cells, postexposure to the compounds, crystal violet staining was used to determine the half-maximal inhibitory concentration (IC50 ), whereas polarization-optical transmitted light differential interference contrast and light microscopy after hematoxylin and eosin (H&E) staining was used to assess morphological changes. l-kyn, Quin, and KA-induced cytotoxicity in all cell lines, with l-kyn being the most cytotoxic compound. l-kyn and KA at IC50 -induced morphological changes in B16 F10, RAW 264.7, and HaCat cell lines, whereas Quin had effects on B16 F10 and RAW 264.7 cells but did not affect HaCat cells. l-kyn, Quin, and KA each display different levels of cytotoxicity, which were cell line specific. l-kyn was shown to be the most potent compound against all cell lines and may offer future treatment strategies when combined with other viable treatments against melanoma.

Keywords: kynurenic acid; kynurenine metabolites; l-kynurenine; melanoma; quinolinic acid.