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Pyrroloquinoline Quinone Induces Cancer Cell Apoptosis via Mitochondrial-Dependent Pathway and Down-Regulating
Zhihui Min1, Lingyan Wang2, Jianjun Jin3
11. 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;
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.
Insights
Pyrroloquinoline quinone (PQQ) demonstrates anti-tumor effects by inducing apoptosis in cancer cells. This compound shows low toxicity to normal cells, suggesting potential for cancer therapy development.
Area of Science:
- Biochemistry
- Cell Biology
- Pharmacology
Background:
- Pyrroloquinoline quinone (PQQ) is recognized for potential anti-tumor properties.
- The precise mechanisms underlying PQQ's effects on cancer cells remain largely unexplored.
Purpose of the Study:
- To investigate the impact of PQQ on the proliferation and apoptosis of solid tumor cell lines.
- To elucidate the molecular pathways involved in PQQ-induced apoptosis.
Main Methods:
- Treatment of A549, Neuro-2A, and HCC-LM3 tumor cell lines with varying concentrations of PQQ.
- Assessment of cell viability, apoptosis markers (ROS, ATP levels, MMP, Bcl-2, caspase-3, MAPK).
- Evaluation of PQQ's effects on normal cell lines (HRPTEpiC, HUVEC).
Main Results:
- PQQ exhibited significant anti-tumor activity against A549 and Neuro-2A cells at low to medium doses.
- PQQ induced apoptosis in tumor cells in a concentration-dependent manner.
- Apoptosis was linked to increased ROS, decreased ATP, mitochondrial dysfunction, altered Bcl-2 and caspase-3 levels, and modified MAPK signaling.
Conclusions:
- PQQ effectively induces mitochondrial-dependent apoptosis in tumor cells.
- PQQ demonstrates selective toxicity, sparing normal cells.
- PQQ shows promise as a potential anti-cancer therapeutic agent.
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