Department of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry, Weinberg 3, 06120 Halle (Saale), Germany.
Department of Engineering and Natural Sciences, University of Applied Sciences Merseburg, Eberhard-Leibnitz-Straße 2, 06217 Merseburg, Germany.
Cells. 2022 Jan 5;11(1):168. doi: 10.3390/cells11010168.
Anthraquinone derivatives exhibit various biological activities, e.g., antifungal, antibacterial and in vitro antiviral activities. They are naturally produced in many fungal and plant families such as Rhamnaceae or Fabaceae. Furthermore, they were found to have anticancer activity, exemplified by mitoxantrone and pixantrone, and many are well known redox-active compounds. In this study, various nature inspired synthetic anthraquinone derivatives were tested against colon, prostate, liver and cervical cancer cell lines. Most of the compounds exhibit anticancer effects against all cell lines, therefore the compounds were further studied to determine their IC-values. Of these compounds, 1,4-bis(benzyloxy)-2,3-bis(hydroxymethyl)anthracene-9,10-dione () exhibited the highest cytotoxicity against PC3 cells and was chosen for a deeper look into its mechanism of action. Based on flow cytometry, the compound was proven to induce apoptosis through the activation of caspases and to demolish the ROS/RNS and NO equilibrium in the PC3 cell line. It trapped cells in the G2/M phase. Western blotting was performed for several proteins related to the effects observed. Compound enhanced the production of PARP and caspase-3. Moreover, it activated the conversion of LC3A/B-I to LC3A/B-II showing that also autophagy plays a role in its mechanism of action, and it caused the phosphorylation of p70 s6 kinase.
蒽醌衍生物表现出多种生物活性，例如抗真菌、抗菌和体外抗病毒活性。它们在许多真菌和植物科中自然产生，如鼠李科或豆科。此外，它们被发现具有抗癌活性，例如米托蒽醌和比沙可啶，并被许多人熟知为氧化还原活性化合物。在这项研究中，各种受自然启发的合成蒽醌衍生物被测试对结肠癌、前列腺癌、肝癌和宫颈癌细胞系的作用。大多数化合物对所有细胞系都表现出抗癌作用，因此进一步研究了这些化合物以确定其 IC 值。在这些化合物中，1,4-双(苄氧基)-2,3-双(羟甲基)蒽-9,10-二酮()对 PC3 细胞表现出最高的细胞毒性，并被选择用于更深入地研究其作用机制。基于流式细胞术，该化合物被证明通过激活半胱天冬酶诱导细胞凋亡，并破坏 PC3 细胞系中的 ROS/RNS 和 NO 平衡。它使细胞停滞在 G2/M 期。进行了 Western blot 实验以研究与观察到的作用相关的几种蛋白质。化合物增强了 PARP 和 caspase-3 的产生。此外，它激活了 LC3A/B-I 向 LC3A/B-II 的转化，表明自噬也在其作用机制中发挥作用，并且导致 p70 s6 激酶的磷酸化。
