Indole-3-carbinol enhances anti-proliferative, but not anti-invasive effects of oxaliplatin in colorectal cancer cell lines.
The primary aim of this study was to determine whether combination of the chemopreventive agent indole-3-carbinol (I3C) with oxaliplatin would decrease proliferative index and invasive potential of human colorectal tumour cells. Combination of the agents resulted in a 170-fold decrease in proliferative capacity in SW480 and SW620 cell lines, which was approximately 6-fold greater than for oxaliplatin alone. Decreased proliferation was attributed to enhanced S-phase cell cycle arrest for SW480, and increased apoptosis for SW620 cells. The combined agents resulted in significantly increased E-cadherin levels in SW480 cells, and beta-catenin levels in both cell lines (assessed by in-cell westerns). In SW480 cells confocal microscopy revealed an increase in membrane-associated beta-catenin levels, with oxaliplatin treatments enhancing nuclear export and cytoplasmic localisation. In SW620 cells, all treatments increased membrane localisation of E-cadherin. Whilst both oxaliplatin and I3C decreased invasive capacity of SW480 cells, this was not further enhanced by the combined treatment.
Howells
Lynne M
LM
Cancer Biomarkers and Prevention Group, Biocentre, University of Leicester, Leicester LE1 7RH, UK. lh28@le.ac.uk
Neal
Christopher P
CP
Brown
Mhairi C
MC
Berry
David P
DP
Manson
Margaret M
MM
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015820:Cadherins / Q000096:biosynthesis; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D004357:Drug Synergism; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology*; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D000077150:Oxaliplatin; D051176:beta Catenin / Q000096:biosynthesis
D000970:Antineoplastic Agents; C495270:CTNNB1 protein, human; D015820:Cadherins; D007211:Indoles; D009944:Organoplatinum Compounds; D051176:beta Catenin; D000077150:Oxaliplatin; C016517:indole-3-carbinol