Basson Charlise, Serem June Cheptoo, Hlophe Yvette Nkondo, Bipath Priyesh
Department of Physiology, School of Medicine, University of Pretoria, Pretoria, South Africa.
Department of Anatomy, School of Medicine, University of Pretoria, Pretoria, South Africa.
Cell Biochem Funct. 2023 Oct;41(7):912-922. doi: 10.1002/cbf.3843. Epub 2023 Sep 3.
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 (IC ), 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 IC -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.
黑色素瘤的转移行为凸显了对特定治疗靶点的需求。化合物,即 l-犬尿氨酸(l-kyn)、喹啉酸(Quin)和犬尿喹啉酸(KA),先前在体外对癌细胞显示出抗增殖和细胞毒性作用。尽管对这些化合物的兴趣日益浓厚,但研究其对黑色素瘤体外作用的研究却很有限。在 B16 F10 黑色素瘤细胞、RAW 264.7 巨噬细胞和 HaCaT 角质形成细胞中,化合物暴露后,使用结晶紫染色来确定半数最大抑制浓度(IC),而苏木精和伊红(H&E)染色后的偏振光透射光微分干涉对比和光学显微镜用于评估形态变化。l-kyn、Quin 和 KA 在所有细胞系中均诱导细胞毒性,其中 l-kyn 是细胞毒性最强的化合物。l-kyn 和 KA 在 IC 时诱导 B16 F10、RAW 264.7 和 HaCaT 细胞系的形态变化,而 Quin 对 B16 F10 和 RAW 264.7 细胞有影响,但不影响 HaCaT 细胞。l-kyn、Quin 和 KA 各自表现出不同程度的细胞毒性,且具有细胞系特异性。l-kyn 被证明是对所有细胞系最有效的化合物,与其他针对黑色素瘤的可行治疗方法联合使用时,可能提供未来的治疗策略。
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