Oncogenic ras alters sensitivity of mouse colonocytes to butyrate and fatty acid mediated growth arrest and apoptosis.
Docosahexaenoic acid (DHA) and butyrate favorably modulate colonocyte proliferation and apoptosis. In order to elucidate how oncogenic Ras modulates responses to these chemopreventive nutrients, we incubated isogenic non-transformed and Ras malignant transformed mouse colon cells with butyrate and DHA or linoleic acid (LA). Combining DHA with 1mM butyrate decreased proliferation relative to LA or no PUFA treatment in both cell lines. At a higher butyrate dose (5mM), caspase 3 activity was elevated to a greater extent in Ras transformed cells. Only non-transformed cells were sensitive to the apoptogenic effects of DHA, indicating that Ras transformation alters sensitivity to dietary chemopreventive agents.
Faculty of Nutrition, Texas A&M University, 2471 TAMU, College Station, TX 77843-2471, USA.
Nancy D
ND
Turner
Jianhu
J
Zhang
Laurie A
LA
Davidson
Joanne R
JR
Lupton
Robert S
RS
Chapkin
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002087:Butyrates / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D003106:Colon / Q000166:cytology / Q000187:drug effects*; D018736:DNA Adducts / Q000378:metabolism; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015525:Fatty Acids, Omega-3; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D011905:Genes, ras / Q000502:physiology*; D019787:Linoleic Acid / Q000494:pharmacology*; D051379:Mice; D014280:Triglycerides / Q000494:pharmacology
D002087:Butyrates; D018736:DNA Adducts; D015525:Fatty Acids, Omega-3; D005231:Fatty Acids, Unsaturated; D014280:Triglycerides; C077446:Pikasol; D004281:Docosahexaenoic Acids; D019787:Linoleic Acid
Non-programmatic