5-aminosalicylic acid enhances anchorage-independent colorectal cancer cell death.
Resistance to anoikis, the cell death triggered by the loss of anchorage to the substratum, is an essential prerequisite in the proliferation and diffusion of colorectal cancer (CRC) cells. We examined whether 5-aminosalicylic acid (5-ASA), a drug that seems to reduce the risk of colitis-associated CRC, enhances CRC cell anoikis. To this end, Colo205 cells were treated with 5-ASA in the presence or absence of inhibitors of caspases (zVAD-fmk) and reactive oxygen species (ROS). We demonstrate that 5-ASA enhances Colo205 cell death. Although 5-ASA induces dissipation of mitochondrial transmembrane potential and caspase-3 activation, zVAD-fmk does not completely prevent the 5-ASA-induced cell death. 5-ASA also enhances the synthesis of ROS. However, inhibitors of ROS reduce the fraction of 5-ASA-induced Colo205 cell death but do not confer protection. In contrast, the 5-ASA-mediated Colo205 cell death is preventable by Bcl-2 over-expression. These data suggest a mechanism by which 5-ASA interferes with colon carcinogenesis.
Fina
Daniele
D
Dipartimento di Medicina Interna, Cattedra di Gastroenterologia, e Centro di Eccellenza per lo studio delle malattie complesse e multifattoriali, Università Tor Vergata, Via Montpellier, 1, 00133 Rome, Italy.
Franchi
Luigi
L
Caruso
Roberta
R
Peluso
Ilaria
I
Naccari
Gian Carlo
GC
Bellinvia
Salvatore
S
Testi
Roberto
R
Pallone
Francesco
F
Monteleone
Giovanni
G
D023102:Anoikis / Q000187:drug effects*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000473:pathology*; D019254:Genes, bcl-2 / Q000187:drug effects; D006801:Humans; D019804:Mesalamine / Q000494:pharmacology*
D000970:Antineoplastic Agents; D019804:Mesalamine