RT Journal Article
SR Electronic
T1 Cell Cycle, Energy Metabolism and DNA Repair Pathways in Cancer Cells are Suppressed by Compound Kushen Injection
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 348102
DO 10.1101/348102
A1 Jian Cui
A1 Zhipeng Qu
A1 Yuka Harata-Lee
A1 Thazin Nwe Aung
A1 Hanyuan Shen
A1 Wei Wang
A1 David L Adelson
YR 2018
UL http://biorxiv.org/content/early/2018/06/21/348102.abstract
AB 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 HEPG2 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 [ADT]/[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.AbbreviationsDSBsdouble strand breaksKu70/Ku80the Ku heterodimer proteins