Raddeanin A 通过调节 MAPK 和 Ras/Raf 信号通路增强自然杀伤细胞对慢性粒细胞白血病细胞的细胞毒性。
Raddeanin A augments the cytotoxicity of natural killer cells against chronic myeloid leukaemia cells by modulating MAPK and Ras/Raf signalling pathways.
发表日期：2024 Aug
作者：
Ming-Ju Hsieh, Jen-Tsun Lin, Yi-Ching Chuang, Yu-Sheng Lo, Chia-Chieh Lin, Hsin-Yu Ho, Mu-Kuan Chen
来源：
Cell Death & Disease
摘要：
自然杀伤 (NK) 细胞疗法是一种正在发展的癌症免疫疗法，涉及从外周血中分离 NK 细胞。然而，由于其数量和活性有限，因此必须显着扩增这些原代 NK 细胞并增强其细胞毒性。在这项研究中，我们研究了 Raddeanin A 如何使用 KHYG-1 细胞增强 NK 活性。结果表明，Raddeanin A 增加了 KHYG-1 细胞中穿孔素、颗粒酶 A 和颗粒酶 B、颗粒溶素和 FasL 等溶细胞分子的表达水平。 Raddeanin A 处理增加 CREB 磷酸化、p65 磷酸化、NFAT1 和乙酰组蛋白 H3 表达。 Raddeanin A 升高 caspase 3 和 PARP 裂解，增加 t-Bid 表达，促进 K562 细胞凋亡。此外，它还降低了 HMGB2、SET 和 Ape1 的表达，损害 DNA 修复过程，导致 K562 细胞不依赖 caspase 死亡。此外，Raddeanin A 在分子水平上增加了 ERK、p38 和 JNK 磷酸化，从而增加了 KHYG-1 细胞中颗粒酶 B 的产量。 Raddeanin A 处理增加 KHYG-1 细胞中 Ras、Raf 磷酸化、MEK 磷酸化、NKG2D、NKp44 和 NKp30 的表达。总的来说，我们的数据表明 Raddeanin A 增强 NK 细胞针对不同癌细胞的细胞毒活性。© 2024 作者。细胞与分子医学基金会和约翰·威利出版的《细胞与分子医学杂志》
Natural killer (NK) cell therapy, a developing approach in cancer immunotherapy, involves isolating NK cells from peripheral blood. However, due to their limited number and activity, it is essential to significantly expand these primary NK cells and enhance their cytotoxicity. In this study, we investigated how Raddeanin A potentiate NK activity using KHYG-1 cells. The results indicated that Raddeanin A increased the expression levels of cytolytic molecules such as perforin, granzymes A and granzymes B, granulysin and FasL in KHYG-1 cells. Raddeanin A treatment increased CREB phosphorylation, p65 phosphorylation, NFAT1 and acetyl-histone H3 expression. Raddeanin A elevated caspase 3 and PARP cleavage, increased t-Bid expression, promoting apoptosis in K562 cells. Furthermore, it reduced the expression of HMGB2, SET and Ape1, impairing the DNA repair process and causing K562 cells to die caspase-independently. Additionally, Raddeanin A increased ERK, p38 and JNK phosphorylation at the molecular level, which increased granzyme B production in KHYG-1 cells. Raddeanin A treatment increased Ras, Raf phosphorylation, MEK phosphorylation, NKG2D, NKp44 and NKp30 expression in KHYG-1 cells. Collectively, our data indicate that Raddeanin A enhances the cytotoxic activity of NK cells against different cancer cells.© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.