Amir Mehdizadeh
1,2, Morteza Bonyadi
3,4, Masoud Darabi
5, Reza Rahbarghazi
5, Soheila Montazersaheb
5, Kobra Velaei
5, Maghsood Shaaker
6, Mohammad-Hossein Somi
3*1 Endocrine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
2 Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
4 Center of Excellence for Biodiversity, Faculty of Natural Sciences, University of Tabriz, Iran
5 Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
6 Department of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
Abstract
Introduction: Cancer cells are critically correlated with lipid molecules, particularly fatty acids, as structural blocks for membrane building, energy sources, and related signaling molecules. Therefore, cancer progression is in direct correlation with fatty acid metabolism. The aim of this study was to investigate the potential effects of common chemotherapeutic agents on the lipid metabolism of hepatocellular carcinoma (HCC) and colorectal cancer (CRC) cells, with a focus on alterations in cellular fatty acid contents.
Methods: Human HepG2 and SW480 cell lines as HCC and CRC cells were respectively cultured in RPMI-1640 medium supplemented with non-toxic doses of 5-fluorouracil and doxorubicin for 72 hours. Oil Red O dye was used to estimate intracellular lipid vacuole intensity. Fatty acid analysis of isolated membrane phospholipids and cytoplasmic triglycerides (TG) was performed by gas-liquid chromatography (GLC) technique.
Results: Oil red O staining represented significantly higher lipid accumulation and density in cancer cells after exposure to the chemotherapeutic agents as compared to non-treated control cells. Doxorubicin and 5-fluorouracil treatment promoted the channeling of saturated fatty acids (SFAs) from phospholipids to triglyceride pool in both HepG2 (+5.91% and +8.50%, P < 0.05, respectively) and SW480 (+37.41% and +5.73%, P < 0.05, respectively) cell lines. However, total polyunsaturated fatty acid content was inversely shifted from TG to phospholipid fraction after doxorubicin and 5-fluorouracil incubation of HepG2 (+58.89% and +29.13%, P < 0.05, respectively) and SW480 (+19.20% and +14.65%, P < 0.05, respectively) cells.
Conclusion: Our data showed that common chemotherapeutic agents of HCC and CRC can induce significant changes in cellular lipid accumulation and distribution of fatty acids through producing highly saturated and unsaturated lipid droplets and membrane lipids, respectively. These metabolic side effects may be associated with gastrointestinal cancers treatment failure.