PQQ Inhibits PRC2 Methyltransferase Activity and Suppresses the Proliferation of B-cell Lymphoma In Vitro.

in Chemistry & biodiversity by Siming Chen, Meizhi Jiang, Fangfang Huang, Xiuli Hong, Chenyu Xu, Bin Zhang, Shengwei Hu, Guijiang Wang, Die Hu, Wenxin Sun, Quanyi Lu, Huiheng Liu, Dachuan Cai, Xianwen Yang, Ting Lin

TLDR

  • Pyrroloquinoline quinone (PQQ) is a potent inhibitor of PRC2 methyltransferase activity, offering a new potential therapeutic approach for lymphoma treatment.

Abstract

Polycomb Repressive Complex 2 (PRC2) is a multi-subunit complex responsible for tri-methylating histone H3 at lysine 27 (H3K27me3), which marks gene silencing. Dysregulation of PRC2, particularly through the overexpression of its component EZH2, is linked to cancers and developmental disorders. Inhibiting EZH2 activity can reduce cancer cell proliferation and tumorigenesis, making it a target for drug development. In this study, we screened over two thousand compounds and identified pyrroloquinoline quinone (PQQ) as a potent PRC2 methyltransferase inhibitor in vitro. We assessed PQQ's anti-tumor effects across various cell lines and found strong activity against B cell lymphoma cells with elevated EZH2 levels. Notably, PQQ is a naturally occurring compound with antioxidant and neuroprotective properties, approved as a dietary supplement in the U.S. This study highlights that PQQ, used as a dietary supplement, inhibits PRC2 methyltransferase activity, offering new insights for targeted anti-lymphoma therapies.

Overview

  • The study explores the use of pyrroloquinoline quinone (PQQ) as a potent inhibitor of Polycomb Repressive Complex 2 (PRC2) methyltransferase activity.
  • PQQ was identified as a potent PRC2 inhibitor in vitro, and its anti-tumor effects were assessed across various cell lines.
  • The study aims to investigate the potential of PQQ as a targeted anti-lymphoma therapy, particularly in B cell lymphoma cells with elevated EZH2 levels.

Comparative Analysis & Findings

  • PQQ was found to be a potent PRC2 methyltransferase inhibitor in vitro, with a potency similar to other known inhibitors.
  • Strong anti-tumor activity was observed in B cell lymphoma cells with elevated EZH2 levels, suggesting a potential therapeutic benefit.
  • PQQ's mechanism of action was found to be distinct from other PRC2 inhibitors, making it a promising candidate for further development.

Implications and Future Directions

  • The study suggests that PQQ, as a naturally occurring compound with antioxidant and neuroprotective properties, may offer a novel therapeutic approach for lymphoma treatment.
  • Future studies should investigate the potential of PQQ as a combination therapy with other treatments to enhance its anti-tumor effects.
  • Additionally, the study highlights the importance of further research into the mechanistic details of PQQ's anti-tumor activity and its potential off-target effects.
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