Cafestol, a diterpene molecule found in coffee, induces leukemia cell death - 01/07/17
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Graphical abstract |
Highlights |
• | Cafestol is cytotoxic to leukemia cells and inhibits their clonogenicity. |
• | Caspase-3 activation, ROS reduction and ΔΨM depolarization are observed in Cafestol-treated leukemia cells. |
• | Cafestol induces differentiation of leukemia cells and stimulates murine CFU-GM. |
• | When in combination, Cafestol increases the Ara-C cytotoxicity against leukemia HL60 cells. |
Abstract |
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.
Le texte complet de cet article est disponible en PDF.Keywords : Cafestol, Leukemia, Apoptosis, Cytotoxicity, Clonogenicity
Plan
Vol 92
P. 1045-1054 - août 2017 Retour au numéro
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