Department of Physiology, School of Medicine, Faculty of Health Sciences, University of Pretoria, Private Bag X323, Gezina, Pretoria 0031, South Africa.
Laboratory for Biological Characterisation of Advanced Materials (LBCAM), TTMI, School of Medicine, Trinity College Dublin, D08 W9R Dublin, Ireland.
Cells. 2022 Oct 26;11(21):3385. doi: 10.3390/cells11213385.
Papaverine (PPV), a benzylisoquinoline alkaloid, extracted from the plant, is currently in clinical use as a vasodilator. Research has shown that PPV inhibits phosphodiesterase 10A (PDE10A,) resulting in the accumulation of cyclic adenosine 3', 5'-monophosphate (cAMP) that affects multiple downstream pathways, including phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt), a mammalian target of rapamycin (mTOR) and vascular endothelial growth factor (VEGF). The accumulation of cAMP can further affect mitochondrial metabolism through the activation of protein kinase A (PKA), which activates the mitochondrial complex I. Literature has shown that PPV exerts anti-proliferative affects in several tumorigenic cell lines including adenocarcinoma alveolar cancer (A549) and human hepatoma (HepG-2) cell lines. Cell cycle investigations have shown varying results with the effects dependent on concentration and cell type with data suggesting an increase in cells occupying the sub-G phase, which is indicative of cell death. These results suggest that PPV may be a beneficial compound to explore for the use in anticancer studies. More insight into the effects of the compound on cellular and molecular mechanisms is needed. Understanding the effects PPV may exert on tumorigenic cells may better researchers' understanding of phytomedicines and the effects of PPV and PPV-derived compounds in cancer.
罂粟碱（PPV）是一种从植物中提取的苄基异喹啉生物碱，目前作为血管扩张剂在临床上使用。研究表明，PPV 抑制磷酸二酯酶 10A（PDE10A），导致环腺苷酸 3'，5'-单磷酸（cAMP）的积累，从而影响多个下游途径，包括磷脂酰肌醇-3-激酶/蛋白激酶 B（PI3K/Akt）、雷帕霉素的哺乳动物靶标（mTOR）和血管内皮生长因子（VEGF）。cAMP 的积累可以通过激活蛋白激酶 A（PKA）进一步影响线粒体代谢，PKA 激活线粒体复合物 I。文献表明，PPV 在包括肺泡腺癌（A549）和人肝癌（HepG-2）细胞系在内的几种致瘤细胞系中发挥抗增殖作用。细胞周期研究结果不一，其作用取决于浓度和细胞类型，数据表明，处于亚 G1 期的细胞增加，这表明细胞死亡。这些结果表明，PPV 可能是一种有益的化合物，可用于抗癌研究。需要更多地了解该化合物对细胞和分子机制的影响。了解 PPV 对致瘤细胞的影响可能会更好地理解植物药以及 PPV 和 PPV 衍生化合物在癌症中的作用。
