Abstract |
The present study was designed to assess the synergistic antitumor effects of anthracenylmethyl homospermidine ( ANTMHspd), a novel polyamine conjugate, with alpha-difluoromethylornithine (DFMO) and to elucidate the mechanism of these effects on human leukemia HL60 cells. Cell proliferation was assessed by the MTT assay. Cell cycle, apoptosis and mitochondria membrane potential ( MMP) were evaluated by flow cytometry. Caspases and cytochrome c were detected by Western Blot analysis. The combination treatment strongly inhibited cell proliferation, induced cell apoptosis and caused an accumulation in the G1 phase with an accompaniment decrease in S phase. Moreover, reduction of MMP, release of cytochrome c and activation of caspase-3 and caspase-9 but not caspase-8 were observed during the combination-mediated apoptosis. All these findings demonstrated that the combination treatment with DFMO and ANTMHspd resulted in synergistic antitumor effects on HL60 cells.
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Authors | Song-qiang Xie, Guang-chao Liu, Yuan-fang Ma, Peng-fei Cheng, Ying-liang Wu, Min-wei Wang, Bian-sheng Ji, Jin Zhao, Chao-jie Wang |
Journal | Toxicology in vitro : an international journal published in association with BIBRA
(Toxicol In Vitro)
Vol. 22
Issue 2
Pg. 352-8
(Mar 2008)
ISSN: 0887-2333 [Print] England |
PMID | 17993255
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anthracenes
- Antineoplastic Agents
- Apoptosis Regulatory Proteins
- Caspase Inhibitors
- Enzyme Inhibitors
- Fluorescent Dyes
- anthracenylmethyl homospermidine
- sym-homospermidine
- Cytochromes c
- Caspases
- Fluorescein-5-isothiocyanate
- Spermidine
- Eflornithine
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Topics |
- Anthracenes
(pharmacology)
- Antineoplastic Agents
(pharmacology)
- Apoptosis
(drug effects)
- Apoptosis Regulatory Proteins
(metabolism, physiology)
- Blotting, Western
- Caspase Inhibitors
- Caspases
(metabolism)
- Cell Cycle
(drug effects)
- Cell Proliferation
(drug effects)
- Cytochromes c
(metabolism)
- Drug Synergism
- Eflornithine
(pharmacology)
- Enzyme Inhibitors
(pharmacology)
- Flow Cytometry
- Fluorescein-5-isothiocyanate
- Fluorescent Dyes
- HL-60 Cells
- Humans
- Membrane Potentials
(drug effects)
- Mitochondrial Membranes
(drug effects)
- Spermidine
(analogs & derivatives, pharmacology)
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