Adu-Amankwaah Francis, Hussan Ayesha, Amenuvor Gershon, Mavumengwana Vuyo, Sitole Lungile
South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Stellenbosch, 7505, South Africa.
Department of Biochemistry, Faculty of Science, University of Johannesburg, Johannesburg, 2006, South Africa.
Metabolomics. 2025 Jan 20;21(1):18. doi: 10.1007/s11306-025-02221-7.
Melanoma is an aggressive form of cancer characterised by its high metabolic adaptability that contributes to drug resistance. To this end, ruthenium complexes have emerged as a promising class of compounds in the discovery of cancer drugs due to their unique chemical properties and potential to overcome some of the limitations of conventional chemotherapy. In our previous study, we synthesised, characterised, and performed cytotoxicity tests of a ruthenium (II) complex (GA113) against the malignant A375 melanoma cell line. Our previous findings revealed favourable cytotoxicity, with an IC value of 8.76 µM which formed the basis current study.
Elucidate the metabolic mechanism of GA113 in malignant A753 melanoma cells.
A two-dimensional gas chromatography time-of-flight mass spectrometry (GCxGC-TOF/MS) cellular metabolomics approach was used, and univariate and multivariate statistical methods were applied to the metabolomics data.
33 metabolites were identified as significant discriminators between GA113-treated and untreated A375 melanoma cells. Changes in 19 of these 33 metabolites were mapped to pantothenate and coenzyme A biosynthesis, citrate cycle, cysteine and methionine metabolism, arginine and proline metabolism, and alanine, aspartate, and glutamate metabolism.
These findings suggest that GA113 exerts its anticancer effects by disrupting essential metabolic pathways in melanoma cells, which presents a promising therapeutic avenue to target melanoma metabolism.
黑色素瘤是一种侵袭性癌症，其特点是具有高代谢适应性，这导致了耐药性。为此，钌配合物因其独特的化学性质以及克服传统化疗某些局限性的潜力，已成为癌症药物发现中一类有前景的化合物。在我们之前的研究中，我们合成、表征并对一种钌（II）配合物（GA113）针对恶性A375黑色素瘤细胞系进行了细胞毒性测试。我们之前的研究结果显示出良好的细胞毒性，IC值为8.76 µM，这构成了当前研究的基础。
阐明GA113在恶性A753黑色素瘤细胞中的代谢机制。
采用二维气相色谱 - 飞行时间质谱（GCxGC - TOF/MS）细胞代谢组学方法，并将单变量和多变量统计方法应用于代谢组学数据。
33种代谢物被确定为GA113处理组和未处理组A375黑色素瘤细胞之间的显著判别物。这33种代谢物中的19种变化与泛酸和辅酶A生物合成、柠檬酸循环、半胱氨酸和甲硫氨酸代谢、精氨酸和脯氨酸代谢以及丙氨酸、天冬氨酸和谷氨酸代谢相关。
这些发现表明，GA113通过破坏黑色素瘤细胞中的关键代谢途径发挥其抗癌作用，这为靶向黑色素瘤代谢提供了一条有前景的治疗途径。
