J Cancer 2014; 5(7):609-624. doi:10.7150/jca.9002
Pyrroloquinoline Quinone Induces Cancer Cell Apoptosis via Mitochondrial-Dependent Pathway and Down-Regulating Cellular Bcl-2 Protein Expression
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;
4. Department of Cardiothoracic Surgery, Tongji Hospital, Tongji University, Shanghai 200065, China;
5. Department of Hematology, Zhongshan Hospital, Fudan University, Shanghai 200032, China;
6. Department of Hematology, Zhongshan Hospital Qingpu Branch, Shanghai, 201700 China.
* These authors contributed equally to this work.
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.
Keywords: pyrroloquinoline quinone (PQQ), apoptosis, MAPK, mitochondrial membrane potential, bcl-2.
Min Z, Wang L, Jin J, Wang X, Zhu B, Chen H, Cheng Y. Pyrroloquinoline Quinone Induces Cancer Cell Apoptosis via Mitochondrial-Dependent Pathway and Down-Regulating Cellular Bcl-2 Protein Expression. J Cancer 2014; 5(7):609-624. doi:10.7150/jca.9002. Available from http://www.jcancer.org/v05p0609.htm