DHA alters expression of target proteins of cancer therapy in chemotherapy resistant SW620 colon cancer cells.
Diets rich in n-3 polyunsaturated fatty acids (PUFAs) have been associated with a reduced risk of several types of cancer. Recent reports have suggested that these PUFAs enhance the cytotoxic effect of cancer chemoradiotherapy. The effect of docosahexaenoic acid (DHA) on key cell cycle regulators and target proteins of cancer therapy was investigated in the human malign colon cancer cell line SW620. Cell cycle check point proteins such as p21 and stratifin (14-3-3 sigma) increased at mRNA and protein level, whereas cell cycle progression proteins such as cell division cycle 25 homolog and cyclin-dependent kinase 1 decreased after DHA treatment. Protein levels of inhibitors of apoptosis family members associated with chemotherapy resistance and cancer malignancy, survivin and livin, decreased after the same treatment: likewise the expression of NF-kappaB. Levels of the proapoptotic proteins phosphorylated p38 MAPK and growth arrest-inducible and DNA damage-inducible gene 153/C/EBP-homologous protein (CHOP) increased. The results indicate that DHA treatment causes simultaneous cell cycle arrest in both the G1 and G2 phase. In conclusion, DHA affects several target proteins of chemotherapy in a favorable way. This may explain the observed enhanced chemosensitivity in cancer cells supplemented with n-3 PUFAs and encourage further studies investigating the role of n-3 PUFAs as adjuvant to chemotherapy and radiotherapy in vivo.
Slagsvold
Jens E
JE
Norwegian University of Science and Technology, Trondheim, Norway.
Pettersen
Caroline H H
CH
Størvold
Gro L
GL
Follestad
Turid
T
Krokan
Hans E
HE
Schønberg
Svanhild A
SA
D017209:Apoptosis; D016203:CDC2 Protein Kinase / Q000032:analysis; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D016193:G1 Phase / Q000187:drug effects; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D051996:Transcription Factor RelA / Q000032:analysis; D020687:cdc25 Phosphatases / Q000032:analysis; D048051:p38 Mitogen-Activated Protein Kinases / Q000032:analysis
D051996:Transcription Factor RelA; D004281:Docosahexaenoic Acids; D016203:CDC2 Protein Kinase; D048051:p38 Mitogen-Activated Protein Kinases; C517009:CDC25C protein, human; D020687:cdc25 Phosphatases