JKMRS Volume 21, No 1, pp 31; Comparison of Metabolic Profiles... | |
---|---|
2017년 03월 20일 / 조회수: 569 | |
Comparison of Metabolic Profiles of Normal and Cancer Cells in Response to Cytotoxic Agents
Sujin Lee, Sunmi Kang and Sunghyouk Park*
Natural Product Research Institute, College of Pharmacy, Seoul National University, Sillim-dong, Gwanak-gu, Seoul, 151-742, Korea
Abstract Together
with radiotherapy, chemotherapy using cytotoxic agents is one of the most
common therapies in cancer. Metabolic changes in cancer cells are drawing much attention
recently, but the metabolic alterations by anticancer agents have not been much
studied. Here, we investigated the effects of commonly used cytotoxic agents on
lung normal cell MRC5 and lung cancer cell A549. We employed cis-plastin,
doxorubicin, and 5-Fluorouracil and compared their effects on the viability and
metabolism of the normal and cancer cell lines. We first established the
concentration of the cytotoxic reagents that give differences in the
viabilities of normal and cancer cell lines. In those conditions, the viability
of A549 decreased significantly, whereas that of MRC5 remained unchanged. To
study the metabolic alterations implicated in the viability differences, we
obtained the metabolic profiles using 1H-NMR spectrometry. The 1H-NMR
data showed that the metabolic changes of A549 cells are more remarkable than
that of MRC5 cells and the effect of 5-FU on the A549 cells is the most
distinct compared to other treatments. Heat map analysis showed that metabolic
alterations under treatment of cytotoxic agents are totally different between
normal and cancer cells. Multivariate analysis and weighted correlation network
analysis (WGCNA) revealed a distinctive metabolite signature and hub
metabolites. Two different analysis tools revealed that the changes of cell
metabolism in response to cytotoxic agents were highly correlated with the
Warburg effect and Reductive lipogenesis, two pathways having important effects
on the cell survival. Taken together, our study addressed the correlation between
the viability and metabolic profiles of MRC5 and A549 cells upon the treatment
of cytotoxic anticancer agents. |
|
첨부파일 | 6_201703_박성혁.pdf |