Title:Guaraná a Caffeine-Rich Food Increases Oxaliplatin Sensitivity of Colorectal HT-29 Cells by Apoptosis Pathway Modulation
VOLUME: 16 ISSUE: 8
Author(s):Francine Carla Cadoná, Alencar Kolinski Machado, Verônica Farina Azzolin, Fernanda Barbisan, Eduardo Bortoluzzi Dornelles, Werner Glanzner, Paulo Bayard Dias Gonçalves, Charles Elias Assmann, Euler Esteves Ribeiro and Ivana Beatrice Mânica da Cruz
Affiliation:I.B.M. da Cruz, Av Roraima 1000, Building 19, Santa Maria-RS, Brazil.
Keywords:Guaraná, HT-29, cancer colorectal, oxaliplatin.
Abstract:We investigated the in vitro effects of guaraná and its main metabolites (caffeine,
theobromine and catechin) on cytotoxicity and cell proliferation on colorectal cancer (CRC) line
HT-29 cells and on oxaliplatin sensitivity. The cells were exposed to different concentrations of
guaraná extract with and without oxaliplatin. The concentrations of bioactive molecules were
also estimated considering their potential proportion on guaraná hydro-alcoholic extract.
Apoptosis effect was analyzed by annexin V quantification using flow cytometry, while apoptosis
pathway gene modulation (p53, Bax/Bcl-2 genes ratio, caspases 8 and 3) was determined by
qRT-PCR analysis. Cells exposed to guaraná at a concentration of 100 μg/mL presented a
similar cytotoxic effect as HT-29 cells treated with oxaliplatin and did not affect the sensitivity
of the drug. Guaraná presented cell anti-proliferative effect and increased anti-proliferative
oxaliplatin sensitivity at all concentrations tested here. Guaraná was able to induce apoptosis
and up-regulate the p53 and Bax/Bcl-2 genes.