Common chemotherapeutic agents modulate fatty acid distribution in human hepatocellular carcinoma and colorectal cancer cells

常见化疗药物调节人类肝细胞癌和结直肠癌细胞中的脂肪酸分布

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作者:Amir Mehdizadeh, Morteza Bonyadi, Masoud Darabi, Reza Rahbarghazi, Soheila Montazersaheb, Kobra Velaei, Maghsood Shaaker, Mohammad-Hossein Somi

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.

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.

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