A novel synthesized 3′, 5′-diprenylated chalcone mediates the proliferation of human leukemia cells by regulating apoptosis and autophagy pathways

作者：Zhang, Yong-Qiang; Wen, Zhong-Hang; Wan, Ke; Yuan, Dongbo; Zeng, Xiaoping; Liang, Guangyi; Zhu, Jianguo^*; Xu, Bixue^*; Luo, Heng^*

来源：Biomedicine & Pharmacotherapy, 2018, 106: 794-804.

DOI：10.1016/j.biopha.2018.06.153

• 3 ',5 '-Diprenylated chalcone
• Leukemia cell
• Apoptosis pathway
• Autophagy pathway

Leukemia is a hematologic malignancy with poor prognosis in humans and chemotherapy is the main strategy for treating leukemia patients. Novel drugs with better selectivity and lower toxicity are required for the treatment of patients. A novel 3',5'-diprenylated chalcone, (E) 1 (2 hydroxy-4-methoxy-3,5-diprenyl) phenyl-3(3- pyridinyl)-propene-1-one (C10) is a potential new anti-leukemia agent. In this study, we investigated the molecular mechanisms of the anti-leukemia effects of C10 on different leukemia cells in vitro. C10 showed strong inhibition of proliferation of the human erythroleukemia cell line HEL and human myeloid leukemia cell line K562, and several cell and flow cytometer assays showed that inhibition by C10 was due to the regulation of gene expression or phosphorylation in the apoptosis and autophagy pathways. The results showed that C10 regulated the expression of Box, c-Myc, Bcl-2, P38/AMPK and ERK 1/2, activated the expression of Caspase-3, -8, and PARP at the protein level in the apoptosis pathway of the two leukemia cell types, and inhibited the expression of erythroleukemia carcinogene Fli-1 in the human erythroleukemia cell line HEL. Additionally,treatment with the compound induced a time-dependent increase in expression of LC 3A/B via inhibiting the AKT-mTOR pathway, which is associated with cell autophagy. Taken together, the above results suggest that the novel synthesized 3',5'-diprenylated chalcone can prevent the growth of leukemia cells by inducing apoptosis and autophagy.

• 出版日期2018-10
• 单位贵州省中国科学院天然产物化学重点实验室; 贵州大学; 贵州省人民医院