Actinomycin D inhibiting K562 cell apoptosis elicited by salvicine but not decreasing its cytotoxicity.
OBJECTIVE
To study the effects of actinomycin D (Act D) on the cytotoxicity and apoptosis elicited by salvicine in human leukemia K562 cells.


METHODS
Growth inhibition of K562 cells was measured by the microculture tetrozolium (MTT) assay. Cell apoptosis was evaluated by fluorescence microscopy, DNA agarose gel electrophoresis, and flow cytometry.


RESULTS
Following exposure of K-562 cells to salvicine plus Act D for 24 h, Act D at the concentrations of 0.04, 0.4, and 4 micromol/L potentiated the cytotoxicity of salvicine 6.25 micromol/L to some degree. The mean growth inhibitory rates went from 8 % up to 69 %, 71 %, and 70 %, respectively. However, the same enhancement of Act D did not continue to emerge at the higher concentrations than salvicine 6.25 micromol/L. Act D enhanced, or at least, did not decrease the cytotoxicity of salvicine against K562 cells. Fluorescence microscopy, DNA agarose gel electrophoresis, and flow cytometry revealed that Act D concentration-dependently inhibited the induction of apoptosis by salvicine in the same cell line.


CONCLUSIONS
The combination of salvicine and Act D in a proper range of concentrations is able to enhance the cytotoxicity of salvicine against K562 cells though inhibiting apoptosis. The other mechanisms of cell death except apoptosis may be implicated in the process.
Division of Antitumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China. jding@mail.shcnc.ac.cn
Chen
C
Qing
Ze-Hong
ZH
Miao
Lin-Jiang
LJ
Tong
Jin-Sheng
JS
Zhang
Jian
J
Ding
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis; D003609:Dactinomycin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020014:K562 Cells / Q000187:drug effects; D009285:Naphthoquinones / Q000494:pharmacology*
D000903:Antibiotics, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D009285:Naphthoquinones; C122096:salvicine; D003609:Dactinomycin