Zheng Zhaoqing, Wu Man, Zhang Juan, Fu Wenwei, Xu Naihan, Lao Yuanzhi, Lin Lan, Xu Hongxi
School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai, China.
Front Oncol. 2019 Jul 17;9:654. doi: 10.3389/fonc.2019.00654. eCollection 2019.
The complexity and multi-target feature of natural compounds have made it difficult to elucidate their mechanism of action (MoA), which hindered the development of lead anticancer compounds to some extent. In this study, we applied RNA-Seq and GSEA transcriptome analysis to rapidly and efficiently evaluate the anticancer mechanisms of neobractatin (NBT), a caged prenylxanthone isolated from the Chinese herb . We found that NBT exerted anti-proliferative effect on various cancer cells and caused both G1/S and G2/M arrest in synchronized cancer cells through its effects on the expression of E2F1 and GADD45α. The animal study further suggested that NBT could reduce tumor burden in HeLa xenograft model with no apparent toxicity. By demonstrating the biological effect of NBT, we provided evidences for further investigations of this novel natural compound with anticancer potential.
天然化合物的复杂性和多靶点特性使其作用机制难以阐明，这在一定程度上阻碍了抗癌先导化合物的开发。在本研究中，我们应用RNA测序和基因集富集分析（GSEA）转录组分析，快速有效地评估了新布拉他丁（NBT）的抗癌机制，NBT是一种从中药中分离出的笼状异戊烯基黄酮。我们发现，NBT对多种癌细胞具有抗增殖作用，并通过影响E2F1和GADD45α的表达，使同步化的癌细胞发生G1/S期和G2/M期阻滞。动物研究进一步表明，NBT可减轻HeLa异种移植模型中的肿瘤负担，且无明显毒性。通过证明NBT的生物学效应，我们为进一步研究这种具有抗癌潜力的新型天然化合物提供了证据。
