Lima Cauê S, Spindola Daniel G, Bechara Alexandre, Garcia Daniel M, Palmeira-Dos-Santos Caroline, Peixoto-da-Silva Janaina, Erustes Adolfo G, Michelin Luis F G, Pereira Gustavo J S, Smaili Soraya S, Paredes-Gamero Edgar, Calgarotto Andrana K, Oliveira Carlos R, Bincoletto Claudia
Departamento de Farmacologia, Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo, São Paulo, Brazil.
Departamento de Bioquímica, Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo (UNIFESP), São Paulo/SP, Brazil.
Biomed Pharmacother. 2017 Aug;92:1045-1054. doi: 10.1016/j.biopha.2017.05.109. Epub 2017 Jun 10.
To evaluate the antitumor properties of Cafestol four leukemia cell lines were used (NB4, K562, HL60 and KG1). Cafestol exhibited the highest cytotoxicity against HL60 and KG1 cells, as evidenced by the accumulation of cells in the sub-G1 fraction, mitochondrial membrane potential reduction, accumulation of cleaved caspase-3 and phosphatidylserine externalization. An increase in CD11b and CD15 differentiation markers with attenuated ROS generation was also observed in Cafestol-treated HL60 cells. These results were similar to those obtained following exposure of the same cell line to cytarabine (Ara-C), an antileukemic drug. Cafestol and Ara-C reduced the clonogenic potential of HL60 cells by 100%, but Cafestol spared murine colony forming unit- granulocyte/macrophage (CFU-GM), which retained their clonogenicity. The co-treatment of Cafestol and Ara-C reduced HL60 cell viability compared with both drugs administered alone. In conclusion, despite the distinct molecular mechanisms involved in the activity of Cafestol and Ara-C, a similar cytotoxicity towards leukemia cells was observed, which suggests a need for prophylactic-therapeutic pre-clinical studies regarding the anticancer properties of Cafestol.
为了评估咖啡醇的抗肿瘤特性，使用了四种白血病细胞系（NB4、K562、HL60和KG1）。咖啡醇对HL60和KG1细胞表现出最高的细胞毒性，这通过亚G1期细胞的积累、线粒体膜电位降低、裂解的半胱天冬酶-3的积累和磷脂酰丝氨酸外化得以证明。在经咖啡醇处理的HL60细胞中还观察到CD11b和CD15分化标志物增加，同时活性氧生成减少。这些结果与将同一细胞系暴露于抗白血病药物阿糖胞苷（Ara-C）后获得的结果相似。咖啡醇和阿糖胞苷使HL60细胞的克隆形成能力降低了100%，但咖啡醇使小鼠集落形成单位-粒细胞/巨噬细胞（CFU-GM）得以保留，其仍具有克隆形成能力。与单独使用两种药物相比，咖啡醇和阿糖胞苷联合治疗降低了HL60细胞的活力。总之，尽管咖啡醇和阿糖胞苷活性所涉及的分子机制不同，但观察到它们对白血病细胞具有相似的细胞毒性，这表明需要对咖啡醇的抗癌特性进行临床前预防性治疗研究。
