| 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. |