Journal Article

Cell cycle, energy metabolism and DNA repair pathways in cancer cells are suppressed by Compound Kushen Injection

Wang, Wei, Nwe Aung, Thazin, Shen, Hanyuan, Adelson, David L., Cui, Jian, Qu, Zhipeng, Harata-Lee, Yuka

2019

Overview

Background 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. Methods 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. Results 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. Conclusions 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.

• Publisher: BioMed Central,BioMed Central Ltd,BMC
• Subject: Alkaloid / Alkaloids / Alkaloids - chemistry / Alkaloids - pharmacology / Analysis / Antineoplastic Agents, Phytogenic - chemistry / Antineoplastic Agents, Phytogenic - pharmacology / Apoptosis / Asian medicine / Biochemistry / Biomedical and Life Sciences / Biomedicine / Cancer / Cancer cells / Cancer genetics / Cancer Research / Cell and molecular biology / Cell cycle / Cell Cycle - drug effects / Cell Cycle - genetics / Cell Line, Tumor / Cyclin / DNA / DNA Breaks, Double-Stranded / DNA repair / DNA Repair - drug effects / Drugs, Chinese Herbal - chemistry / Drugs, Chinese Herbal - pharmacology / Energy Metabolism - drug effects / Gene expression / Gene Expression Regulation, Neoplastic - drug effects / Genes / Glucose / Health Promotion and Disease Prevention / Humans / Ku70 / Ku80 / Lactates / Matrine / Medicine/Public Health / Oncology / Proteins / Quinolizines - chemistry / Quinolizines - pharmacology / Research Article / Smilax - chemistry / Surgical Oncology / Traditional Chinese medicine