Apoptotic effect of pyrroloquinoline quinone on chondrosarcoma cells through activation of the mitochondrial caspase‑dependent and caspase‑independent pathways

Wu,Ronghuan; Pan,Jun; Shen,Miaoda; Xing,Chunyang

doi:10.3892/or.2018.6569

Apoptotic effect of pyrroloquinoline quinone on chondrosarcoma cells through activation of the mitochondrial caspase‑dependent and caspase‑independent pathways

Authors:
- Ronghuan Wu
- Jun Pan
- Miaoda Shen
- Chunyang Xing
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Affiliations: Department of Orthopedics, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China
Published online on: July 12, 2018 https://doi.org/10.3892/or.2018.6569
Pages: 1614-1620

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Abstract

Chondrosarcomas are malignant tumors of the bone that exhibit resistance to chemotherapy and radiation. Pyrroloquinoline quinone (PQQ) is a bacterial redox co‑factor 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 concentration‑dependent and time‑dependent manner following PQQ treatment, but this effect was not significant in normal cells. Co‑immunoprecipitation assays showed that the binding of Smac to X‑linked inhibitor‑of‑apoptosis protein (XIAP) was significantly increased and the binding of XIAP with caspase‑3 was significantly decreased following PQQ treatment. This was accompanied by a decrease in the levels of caspase‑1 and procaspase‑3, 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 caspase‑dependent apoptotic pathways in the effect of PQQ. Furthermore, the cytoplasmic and nuclear levels of apoptosis‑inducing factor (AIF) were increased and its mitochondrial levels were decreased, and similar results were obtained for endonuclease G. Thus, the role of caspase‑independent 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 caspase‑dependent and caspase‑independent pathways. Thus, the proteins involved in these pathways may have potential as antitumor treatment targets for chondrosarcoma.

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