Zhuang Jianjian, Yin Juxin, Xu Chaojian, Jiang Mengmeng, Lv Shaowu
Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, College of Life Science, Jilin University Changchun 130000 China
Research Centre for Analytical Instrumentation, Institute of Cyber-Systems and Control, State Key Laboratory of Industrial Control Technology, Zhejiang University Hangzhou Zhejiang Province 310058 P. R. China.
RSC Adv. 2019 Nov 28;9(67):39124-39132. doi: 10.1039/c9ra08049j. eCollection 2019 Nov 27.
Autophagy is an important mechanism for cell death regulation. To improve the anticancer effect during the treatment of leukemia and promote the apoptosis of leukemic cells, it is important to define the relationship between autophagy and apoptosis. A key bioactive compound in traditional Chinese medicine, 20(s)-Ginsenoside (GRh2), demonstrated an advancement in leukemia treatment. Blue LED therapy (BL) is a physical treatment method that can induce leukemic cell death. In this study, we tested the effect of 20(s)-GRh2, BL, and their combination (BL-GRh2) on the activation of leukemic cell apoptosis and autophagy. Both treatments, whether used individually or simultaneously, induce apoptosis through the induction of reactive oxygen species (ROS), disrupted mitochondrial membrane potential (MMP) and regulated the expression of apoptosis-related genes and proteins. Furthermore, using western blotting to analyze the autophagy markers LC3B and P62, we detected the activation of autophagy. In cells treated with autophagy inhibitor 3-MA, both autophagy and apoptosis were inhibited, either by BL alone or by BL-GRh2. However, apoptosis in 20(s)-GRh2-treated cells was enhanced. In cells treated with apoptosis suppressor Z-VAD-FMK, autophagy was inhibited in the BL and BL-GRh2-treated cells, although it was enhanced in cells treated with 20(s)-GRh2 alone. Moreover, we observed a stronger induction of apoptosis by BL-GRh2 in myeloid leukemia cells. Our data indicate that autophagy induced by different factors can play diverse roles on the same cells. Our results also indicate that the combination of traditional Chinese medicine with physical therapy may be a new strategy for anti-cancer therapy.
自噬是细胞死亡调控的重要机制。为提高白血病治疗过程中的抗癌效果并促进白血病细胞凋亡，明确自噬与凋亡之间的关系至关重要。中药中的一种关键生物活性化合物，20(S)-人参皂苷（GRh2），在白血病治疗方面取得了进展。蓝光LED疗法（BL）是一种可诱导白血病细胞死亡的物理治疗方法。在本研究中，我们测试了20(S)-GRh2、BL及其联合应用（BL-GRh2）对白血病细胞凋亡和自噬激活的影响。两种治疗方法，无论是单独使用还是同时使用，均通过诱导活性氧（ROS）、破坏线粒体膜电位（MMP）并调节凋亡相关基因和蛋白质的表达来诱导凋亡。此外，通过蛋白质印迹法分析自噬标志物LC3B和P62，我们检测到了自噬的激活。在用自噬抑制剂3-MA处理的细胞中，单独使用BL或BL-GRh2均可抑制自噬和凋亡。然而，20(S)-GRh2处理的细胞中凋亡增强。在用凋亡抑制剂Z-VAD-FMK处理的细胞中，BL和BL-GRh2处理的细胞中自噬受到抑制，而单独用20(S)-GRh2处理的细胞中自噬增强。此外，我们观察到BL-GRh2对髓系白血病细胞凋亡的诱导作用更强。我们的数据表明，不同因素诱导的自噬可在同一细胞上发挥不同作用。我们的结果还表明，中药与物理疗法的联合应用可能是抗癌治疗的一种新策略。
