Acetylsalicylic acid strengthens the effects of ANISpm against hepatocellular carcinoma and its molecular mechanism.
- Author:
Song-qiang XIE
1
;
Lei-lei ZHANG
;
Tao YANG
;
Ying MA
;
Ya-hong ZHANG
;
Qian LI
;
Jian-hong WANG
;
Jin ZHAO
;
Chao-jie WANG
Author Information
1. Institute of Chemistry and Biology, Henan University, Kaifeng 475001, China.
- Publication Type:Journal Article
- MeSH:
Acetyltransferases;
metabolism;
Animals;
Antineoplastic Agents;
pharmacology;
Apoptosis;
drug effects;
Aspirin;
pharmacology;
Caspase 8;
metabolism;
Caspase 9;
metabolism;
Cell Line, Tumor;
Cell Proliferation;
drug effects;
Drug Synergism;
Female;
Hep G2 Cells;
Humans;
Liver Neoplasms, Experimental;
pathology;
Membrane Potential, Mitochondrial;
drug effects;
Mice;
Naphthalimides;
chemical synthesis;
metabolism;
pharmacology;
Neoplasm Transplantation;
Polyamines;
chemical synthesis;
metabolism;
pharmacology;
Random Allocation;
Spermine;
chemical synthesis;
metabolism;
pharmacology;
Tumor Burden;
drug effects;
Up-Regulation
- From:
Acta Pharmaceutica Sinica
2011;46(9):1045-1050
- CountryChina
- Language:Chinese
-
Abstract:
The objective of this study is to examine the effects of ANISpm, a novel polyamine naphthalimide conjugate, with acetylsalicylic acid against hepatocellular carcinoma in vivo and in vitro and elucidate its potential molecular mechanism. The proliferation inhibition was detected by MTT assay. Cell apoptosis, intracellular fluorescence intensity and mitochondrial membrane potential (MMP) were detected by high content screening (HCS) analysis. Polyamines content was analyzed by reverse-phase high performance liquid chromatography Protein expression levels were quantified by Western blotting assay. The combination treatment strongly inhibited cell proliferation, induced cell apoptosis in HepG2 cells and H22 hepatoma cells, which was mediated by enhanced ANISpm uptake via up-regulation of spermidine/spermine N1-acetyltransferase (SSAT) and depression of intracellular polyamine. Furthermore, this synergistic apoptosis was involved in mitochondria and death-receptor signal pathway. All these findings demonstrated that the combination treatment with acetylsalicylic acid and ANISpm resulted in synergistic antitumor effects on hepatoma cells. Thus, combination therapy with these agents may be useful as a potential template for the development of better chemotherapeutic strategy against hepatoma.
