Tuzimski Tomasz, Petruczynik Anna, Plech Tomasz, Kaproń Barbara, Makuch-Kocka Anna, Szultka-Młyńska Małgorzata, Misiurek Justyna, Buszewski Bogusław
Department of Physical Chemistry, Medical University of Lublin, Chodźki 4a, 20-093 Lublin, Poland.
Department of Inorganic Chemistry, Medical University of Lublin, Chodźki 4a, 20-093 Lublin, Poland.
Molecules. 2021 Mar 20;26(6):1738. doi: 10.3390/molecules26061738.
Melanoma is an enormous global health burden, and should be effectively addressed with better therapeutic strategies. Therefore, new therapeutic agents are needed for the management of this disease. The aim of this study was the investigation of cytotoxic activity of some isoquinoline alkaloid standards and extracts obtained from -collected before, during, and after flowering-against three different human melanoma cells (A375, G361, SK-MEL-3). The cytotoxicity of these extracts was not previously tested on these melanoma cell lines. Determination of alkaloid contents was performed by HPLC-DAD using Polar RP column and mobile phase containing acetonitrile, water, and 1-butyl-3-methylimidazolium tetrafluoroborate. The cytotoxicity of alkaloid standards was investigated by determination of cell viability and calculation of IC values. Significant differences were observed in the alkaloids content and cytotoxic activity of the extracts, depending on the season of collection of the plant material. In the extracts high contents of sanguinarine (from 4.8543 to 9.5899 mg/g of dry plant material) and chelerythrine (from 42.7224 to 6.8722 mg/g of dry plant material) were found. For both of these alkaloids, very high cytotoxic activity against the tested cell lines were observed. The IC values were in the range of 0.11-0.54 µg/mL for sanguinarine and 0.14 to 0.46 µg/mL for chelerythrine. IC values obtained for extracts against all tested cell lines were also very low (from 0.88 to 10.96 µg/mL). Cytotoxic activity of alkaloid standards and extracts were compared with the cytotoxicity of anticancer drugs-etoposide, cisplatin, and hydroxyurea. In all cases except the one obtained for cisplatin against A375, which was similar to that obtained after flowering against the same cell line, IC values obtained for anticancer drugs were higher than the IC values obtained for sanguinarine, chelerythrine, and extracts. Our results showed that extracts and isoquinoline alkaloids, especially sanguinarine and chelerythrine, could be recommended for further in vivo experiments in order to confirm the possibility of their application in the treatment of human melanomas.
黑色素瘤是一项巨大的全球健康负担，需要采用更好的治疗策略加以有效应对。因此，需要新的治疗药物来管理这种疾病。本研究的目的是调查一些异喹啉生物碱标准品以及从[在开花前、开花期间和开花后采集的]植物中获得的提取物对三种不同人类黑色素瘤细胞（A375、G361、SK-MEL-3）的细胞毒活性。这些提取物的细胞毒性此前未在这些黑色素瘤细胞系上进行过测试。使用极性反相柱和含有乙腈、水以及四氟硼酸1-丁基-3-甲基咪唑鎓的流动相，通过高效液相色谱-二极管阵列检测法（HPLC-DAD）测定生物碱含量。通过测定细胞活力和计算IC值来研究生物碱标准品的细胞毒性。根据植物材料的采集季节，提取物的生物碱含量和细胞毒活性存在显著差异。在提取物中发现了高含量的血根碱（从4.8543至9.5899毫克/克干植物材料）和白屈菜红碱（从42.7224至6.8722毫克/克干植物材料）。对于这两种生物碱，均观察到对测试细胞系具有非常高的细胞毒活性。血根碱的IC值在0.11 - 0.54微克/毫升范围内，白屈菜红碱的IC值在0.14至0.46微克/毫升范围内。提取物对所有测试细胞系获得的IC值也非常低（从0.88至10.96微克/毫升）。将生物碱标准品和提取物的细胞毒活性与抗癌药物依托泊苷、顺铂和羟基脲的细胞毒性进行了比较。除了顺铂对A375获得的结果与开花后对同一细胞系获得的结果相似外，在所有情况下，抗癌药物获得的IC值均高于血根碱、白屈菜红碱和提取物获得的IC值。我们的结果表明，提取物和异喹啉生物碱，尤其是血根碱和白屈菜红碱，可推荐用于进一步的体内实验，以确认它们在治疗人类黑色素瘤中的应用可能性。
