Jakimiuk Katarzyna, Szoka Łukasz, Surażyński Arkadiusz, Tomczyk Michał
Department of Pharmacognosy, Faculty of Pharmacy with the Division of Laboratory Medicine, Medical University of Białystok, ul. Mickiewicza 2a, 15-230 Białystok, Poland.
Department of Medicinal Chemistry, Euroregional Center of Pharmacy, Faculty of Pharmacy with the Division of Laboratory Medicine, Medical University of Białystok, ul. Mickiewicza 2d, 15-222 Białystok, Poland.
Cancers (Basel). 2024 Jan 23;16(3):487. doi: 10.3390/cancers16030487.
Skin cancers are a dominant type of cancer that impacts millions per year. Cancer is a heterogeneous disease triggered by the irreversible impairment of cellular homeostasis and function. In this study, we investigated the activity of 37 structurally diverse flavonoids to find potentially active substances using two melanoma cell lines: C32 and A375. First, the cytotoxic potential and DNA biosynthesis inhibition of flavonoids were tested to determine the most active compounds in cancer and normal cells. Second, the molecular mechanism of the anticancer activity of flavonoids was elucidated using Western blot and immunofluorescence analyses. Compounds , , , and reduced the viability of A375 and C32 cell lines via the intrinsic and extrinsic pathways of apoptosis, whereas and acted in a higher degree via the inhibition of DNA biosynthesis. In our experiment, we demonstrated the anticancer activity of compound (5,6-dihydroxyflavone) for the first time. The in vitro studies pointed out the importance of the flavonoid core in hydroxyl groups in the search for potential drugs for amelanotic melanoma.
皮肤癌是一种主要的癌症类型,每年影响数百万人。癌症是一种异质性疾病,由细胞稳态和功能的不可逆损害引发。在本研究中,我们使用两种黑色素瘤细胞系C32和A375,研究了37种结构各异的黄酮类化合物的活性,以寻找潜在的活性物质。首先,测试黄酮类化合物的细胞毒性潜力和DNA生物合成抑制作用,以确定癌症细胞和正常细胞中最具活性的化合物。其次,使用蛋白质免疫印迹和免疫荧光分析阐明黄酮类化合物抗癌活性的分子机制。化合物、、、和通过凋亡的内在和外在途径降低了A375和C32细胞系的活力,而和通过抑制DNA生物合成发挥了更高程度的作用。在我们的实验中,我们首次证明了化合物(5,6-二羟基黄酮)的抗癌活性。体外研究指出了黄酮类化合物核心中羟基在寻找无黑色素黑色素瘤潜在药物方面的重要性。