[Antineoplastic effect of valproic acid and trichostatin on HL-60 and K562 cells].
The objective of this study was to investigate antineoplastic effects of valproic acid (VPA) and trichostatin (TSA) on HL-60 and K562 cells in vitro, and the synergic effects of VPA or TSA in combination with ATRA. The inhibitory effects of VPA, TSA and ATRA in various concentrations and different combinations on proliferation of HL-60 and K562 cells were observed by cell growth curves, 50% inhibitory concentration (IC(50)), as well as inhibition of leukemia colony growth at different time points. The characteristics of cell differentiation or apoptosis were analyzed by cytochemical staining, differentiation antigen detection, cell cycle assay and A(NBT)/A(MMT) value determination. The results showed that HL-60 cell had a lower IC(50) of VPA and TSA compared with K562 cells. ATRA could significantly enhance the inhibition of VPA, TSA on clonegenicity of HL-60 cells and inhibition of VPA on clonegenicity of K562 cells. HL-60 cells treated with VPA displayed the phenotype of neutrophilic like cells, and showed the increases of NBT reduction rate and CD11b expression. No evidence for K562 differentiation was found. It is concluded that both VPA and TSA inhibit HL-60 cells growth in vitro. VPA induces differentiation of HL-60 cells to granulocyte. VPA and TSA have a moderate anti-proliferative effect on K562 cells. None of these agents induces K562 cell differentiation.
Liu
Heng
H
Department of Pediatric Hematology and Oncology, The West China Second University Hospital, Sichuan Univesity, Chengdu 610041, China.
Fu
Ren-Yi
RY
Li
Feng-Yi
FY
Zhu
Yi-Ping
YP
Wang
Xiao-Yang
XY
Mao
Yong-Qiu
YQ
Wu
Xue-Zhen
XZ
Zhou
Chen-Yan
CY
D000970:Antineoplastic Agents / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects*; D004357:Drug Synergism; D018922:HL-60 Cells; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D020014:K562 Cells; D014635:Valproic Acid / Q000494:pharmacology*
D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; C012589:trichostatin A; D014635:Valproic Acid