Apoptotic effect of pyrroloquinoline quinone on chondrosarcoma cells through activation of the mitochondrial caspasedependent and caspaseindependent pathways.
Oncol Rep
; 40(3): 1614-1620, 2018 Sep.
Article
em En
| MEDLINE
| ID: mdl-30015942
ABSTRACT
Chondrosarcomas are malignant tumors of the bone that exhibit resistance to chemotherapy and radiation. Pyrroloquinoline quinone (PQQ) is a bacterial redox cofactor and antioxidant that has been found to induce apoptosis in various cancer cells. This study investigated the role of PQQ in cell apoptosis of chondrosarcoma cells and the underlying pathways involved. We confirmed that PQQ was cytotoxic to chondrosarcoma SW1353 cells by a cell cytotoxicity assay. Furthermore, flow cytometry showed that the number of apoptotic cells increased in a concentrationdependent and timedependent manner following PQQ treatment, but this effect was not significant in normal cells. Coimmunoprecipitation assays showed that the binding of Smac to Xlinked inhibitorofapoptosis protein (XIAP) was significantly increased and the binding of XIAP with caspase3 was significantly decreased following PQQ treatment. This was accompanied by a decrease in the levels of caspase1 and procaspase3, as demonstrated by western blot analysis. Western blotting also showed that the level of cytochrome c in the mitochondria was decreased and its level in the cytoplasm was increased. These findings indicate the role of caspasedependent apoptotic pathways in the effect of PQQ. Furthermore, the cytoplasmic and nuclear levels of apoptosisinducing factor (AIF) were increased and its mitochondrial levels were decreased, and similar results were obtained for endonuclease G. Thus, the role of caspaseindependent pathways was also demonstrated. Finally, in vivo tumor implantation experiments showed that PQQ was able to inhibit tumor growth in mice with chondrosarcoma. These findings demonstrated that PQQ induced apoptosis in human chondrosarcoma cells by activating mitochondrial caspasedependent and caspaseindependent pathways. Thus, the proteins involved in these pathways may have potential as antitumor treatment targets for chondrosarcoma.
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias Ósseas
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Condrossarcoma
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Apoptose
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Caspases
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Cofator PQQ
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Mitocôndrias
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article