title: Pyrroloquinoline Quinone Induces Cancer Cell Apoptosis via Mitochondrial-Dependent Pathway and Down-Regulating Cellular Bcl-2 Protein Expression.
abstract: Pyrroloquinoline quinone (PQQ) has been reported as a promising agent that might contribute to tumor cell apoptosis and death, yet little is known on its mechanisms. In current study, the effect of PQQ on cell proliferation and mitochondrial-dependent apoptosis were examined in 3 solid tumor cell lines (A549, Neuro-2A and HCC-LM3). PQQ treatment at low to medium dosage exhibited potent anti-tumor activity on A549 and Neuro-2A cells, while had comparably minimal impact on the viabilities of 2 human normal cell lines (HRPTEpiC and HUVEC). The apoptosis of the 3 tumor cell lines induced by PQQ were increased in a concentration-dependent manner, which might be attributed to the accumulation of intracellular reactive oxygen species (ROS), decline in ATP levels and dissipation of mitochondrial membrane potential (MMP), in conjunction with down-regulation of Bcl-2 protein expression, up-regulation of activated caspase-3, and disturbed phosphorylated MAPK protein levels. PQQ induced tumor cells apoptosis was significantly alleviated by pan-caspase inhibitor Z-VAD-FMK. The present work highlights the potential capability of PQQ as an anti-tumor agent with low toxicity towards normal cells through activating mitochondrial-dependent apoptosis pathways, and warrants its development for cancer therapy.
authors.affiliation: 1. Biomedical Research Center, Zhongshan Hospital, Fudan University, Shanghai 200032, China; ; 2. Biomedical Research Center, Zhongshan Hospital Qingpu Branch, Shanghai, 201700 China; ; 3. Shanghai key laboratory of organ transplantation, Shanghai, 200032, China;
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Min
authors.affiliation: 1. Biomedical Research Center, Zhongshan Hospital, Fudan University, Shanghai 200032, China;
authors.forename: Lingyan
authors.initials: L
authors.lastname: Wang
authors.affiliation: 1. Biomedical Research Center, Zhongshan Hospital, Fudan University, Shanghai 200032, China; ; 2. Biomedical Research Center, Zhongshan Hospital Qingpu Branch, Shanghai, 201700 China;
authors.forename: Jianjun
authors.initials: J
authors.lastname: Jin
authors.affiliation: 1. Biomedical Research Center, Zhongshan Hospital, Fudan University, Shanghai 200032, China; ; 2. Biomedical Research Center, Zhongshan Hospital Qingpu Branch, Shanghai, 201700 China; ; 3. Shanghai key laboratory of organ transplantation, Shanghai, 200032, China;
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Wang
authors.affiliation: 1. Biomedical Research Center, Zhongshan Hospital, Fudan University, Shanghai 200032, China;
authors.forename: Bijun
authors.initials: B
authors.lastname: Zhu
authors.affiliation: 4. Department of Cardiothoracic Surgery, Tongji Hospital, Tongji University, Shanghai 200065, China;
authors.forename: Hao
authors.initials: H
authors.lastname: Chen
authors.affiliation: 1. Biomedical Research Center, Zhongshan Hospital, Fudan University, Shanghai 200032, China; ; 3. Shanghai key laboratory of organ transplantation, Shanghai, 200032, China; ; 5. Department of Hematology, Zhongshan Hospital, Fudan University, Shanghai 200032, China; ; 6. Department of Hematology, Zhongshan Hospital Qingpu Branch, Shanghai, 201700 China.
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Cheng
keywords: MAPK; apoptosis; bcl-2.; mitochondrial membrane potential; pyrroloquinoline quinone (PQQ)