Fusarubin and Anhydrofusarubin Isolated from A Cladosporium Species Inhibit Cell Growth in Human Cancer Cell Lines
Fusarubin and Anhydrofusarubin Isolated from A Cladosporium Species Inhibit Cell Growth in Human Cancer Cell Lines
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DOI：
10.3390/toxins11090503
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发表时间：
2019-09-01
期刊：
影响因子：
4.2
通讯作者：
Delfino, Domenico, V
中科院分区：
文献类型：
--
作者：
Adorisio, Sabrina;Fierabracci, Alessandra;Delfino, Domenico, V
枝孢菌属是生长在有机物上的内生真菌，被认为是食品污染物。采用柱层析法从萝芙木叶内的枝孢属植物中分离得到具有抗菌和抗肿瘤作用的萘醌类镰刀菌红素（FUS）和脱水镰刀菌红素（AFU）。在急性髓性白血病（OCI-AML 3）和其他血液肿瘤细胞系（HL-60、U937和Jurkat）中评估了FUS和AFU对细胞生长的影响。用FUS或AFU处理减少了OCI-AML 3细胞的数量，如通过血细胞计数器所评估的。流式细胞术分析表明，这种影响伴随着细胞周期进程的各种障碍。FUS（20或10 μ g/mL）显著降低S期细胞的百分比，增加G2/M期细胞的百分比，而AFU（50和25 μ g/mL）增加G 0/G1期细胞的百分比，降低S期和G2/M期细胞的百分比。这两种物质在较高浓度下均显著增加细胞凋亡。FUS的作用比AFU的作用更强，FUS以p53依赖的方式上调p21表达，如通过Western印迹分析检测到的，可能是ERK磷酸化降低和p38表达增加（两者都增加p21稳定性）的结果。FUS还降低Akt磷酸化，并导致Fas配体产生和caspase-8/3依赖性凋亡增加。这些结果表明，FUS和AFU抑制增殖和增加细胞凋亡来源于血液癌症的细胞系。
Cladosporium species are endophytic fungi that grow on organic matter and are considered food contaminants. The anti-microbial and anti-tumor naphthoquinones fusarubin (FUS) and anhydrofusarubin (AFU) were isolated using column chromatography from a Cladosporium species residing inside Rauwolfia leaves. The impact of FUS and AFU on cell growth was assessed in acute myeloid leukemia (OCI-AML3) and other hematologic tumor cell lines (HL-60, U937, and Jurkat). Treatment with FUS or AFU reduced the number of OCI-AML3 cells as evaluated by a hemocytometer. Flow cytometry analyses showed that this effect was accompanied by diverse impairments in cell cycle progression. Specifically, FUS (20 or 10 mu g/mL significantly decreased the percentage of cells in S phase and increased the percentage of cells in G2/M phase, whereas AFU increased the percentage of cells in G0/G1 phase (50 and 25 mu g/mL) and decreased the percentage of cells in S (50 mu g/mL) and G2/M (50 and 25 mu g/mL) phases. Both substances significantly increased apoptosis at higher concentrations. The effects of FUS were more potent than those of AFU, with FUS up-regulating p21 expression in a p53-dependent manner, as detected by Western blot analyses, likely the consequence of decreased ERK phosphorylation and increased p38 expression (both of which increase p21 stability). FUS also decreased Akt phosphorylation and resulted in increased Fas ligand production and caspase-8/3-dependent apoptosis. These results suggest that FUS and AFU inhibit proliferation and increase apoptosis in cell lines derived from hematological cancers.