Department of Molecular and Biomedical Science, The University of Adelaide, North Terrace, Adelaide, 5005, South Australia, Australia.
Zhendong Australia - China Centre for Molecular Chinese Medicine, The University of Adelaide, North Terrace, Adelaide, 5005, South Australia, Australia.
BMC Cancer. 2019 Jan 24;19(1):103. doi: 10.1186/s12885-018-5230-8.
In this report we examine candidate pathways perturbed by Compound Kushen Injection (CKI), a Traditional Chinese Medicine (TCM) that we have previously shown to alter the gene expression patterns of multiple pathways and induce apoptosis in cancer cells.
We have measured protein levels in Hep G2 and MDA-MB-231 cells for genes in the cell cycle pathway, DNA repair pathway and DNA double strand breaks (DSBs) previously shown to have altered expression by CKI. We have also examined energy metabolism by measuring [ADP]/[ATP] ratio (cell energy charge), lactate production and glucose consumption. Our results demonstrate that CKI can suppress protein levels for cell cycle regulatory proteins and DNA repair while increasing the level of DSBs. We also show that energy metabolism is reduced based on reduced glucose consumption and reduced cellular energy charge.
Our results validate these pathways as important targets for CKI. We also examined the effect of the major alkaloid component of CKI, oxymatrine and determined that it had no effect on DSBs, a small effect on the cell cycle and increased the cell energy charge.
Our results indicate that CKI likely acts through the effect of multiple compounds on multiple targets where the observed phenotype is the integration of these effects and synergistic interactions.
在本报告中，我们研究了候选途径被苦参注射液（CKI）干扰的情况，CKI 是一种中药，我们之前的研究表明它可以改变多种途径的基因表达模式，并诱导癌细胞凋亡。
我们已经测量了 HepG2 和 MDA-MB-231 细胞中细胞周期途径、DNA 修复途径和 DNA 双链断裂（DSBs）的基因的蛋白水平，这些基因之前已经被 CKI 改变了表达。我们还通过测量 [ADP]/[ATP] 比（细胞能量电荷）、乳酸生成和葡萄糖消耗来检查能量代谢。我们的结果表明，CKI 可以抑制细胞周期调节蛋白和 DNA 修复的蛋白水平，同时增加 DSBs 的水平。我们还表明，能量代谢降低是基于葡萄糖消耗减少和细胞能量电荷降低。
我们的结果验证了这些途径是 CKI 的重要靶点。我们还研究了 CKI 的主要生物碱成分氧化苦参碱对 DSBs 的影响，结果表明它对 DSBs 没有影响，对细胞周期有轻微影响，增加了细胞能量电荷。
我们的结果表明，CKI 可能通过多种化合物对多个靶点的作用来发挥作用，观察到的表型是这些作用的整合和协同相互作用的结果。
