Growth-inhibitory and apoptosis-inducing effects of andrographolide on acute lymphoblastic leukemia cells |
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Authors: | LI Xiao-wen ZHOU Yue-han DENG Jian-zhi LUO Zhen-hua JIANG Hai-jian ZHANG Man-li QIN Chu-ling |
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Affiliation: | 1.Guilin Medical University, Guilin 541100, China;2.Guilin University of Technology, Guilin 541004, China. |
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Abstract: | AIM To explore the effect of andrographolide (AND) on the growth and apoptosis of acute lymphoblastic leukemia (ALL) cells. METHODS CCK-8 assay was used to assess the viability of human acute lymphoblastic leukemia CEM-C1 cells treated with AND for 12 h, 24 h and 48 h. The cell morphological changes were observed by Wright-Giemsa staining. The cell apoptosis was detected by flow cytometry with annexin V-FITC/propidium iodide (PI) staining, and the cell cycle was examined by flow cytometry with PI staining. The expression levels of apoptosis-related proteins were examined by Western blot. The mitochondrial membrane potential (MMP) of the cells was determined by JC-1 assay. RESULTS The results of CCK-8 assay indicated that AND inhibited the viability of CEM-C1 cells in a dose- and time-dependent manner. After administration of AND for 24 h, CEM-C1 cells shrank, the cytoplasm turned red and the cell numbers were significantly reduced. Incubation of AND for 24 h resulted in G2-phase arrest and apoptosis. Treatment with AND for 24 h increased the protein levels of cleaved caspase-3, cleaved caspase-7 and Bax, and down-regulated Bcl-2 in the CEM-C1 cells (P<0.05). The ratios of cleaved caspase-3/caspase-3, cleaved caspase-7/caspase-7 and Bax/Bcl-2 were elevated with the increase in the concentration of AND. Collapsed MMP in CEM-C1 cells was observed after AND administration for 24 h. Treatment with AND in vivo suppressed the growth of the xenograft tumor and increased the protein level of cleaved caspase-3. CONCLUSION Andrographolide exerts growth-inhibitory and apoptosis-inducing effects on ALL cells both in vitro and in vivo. |
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Keywords: | Acute lymphoblastic leukemia Andrographolide Cell growth Apoptosis Mitochondrial membrane potential |
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