The impact of superoxide-peroxide hydrogen imbalance on chemotherapy response of colorectal cancer cells: an in vitro study

8^th Euro Global Summit on Cancer Therapy

November 03-05, 2015 Valencia, Spain

Alencar Kolinski Machado, Veronica Farina Azzolin, Francine Carla Cadona, Fernanda Barbisan, Eduardo Bortoluzzi Dornelles, Beatriz da Silva Rosa and Ivana Beatrice Manica da Cruz

Federal University of Santa Maria, 1000 Roraima av., 97105-900, RS, Brazil.

Posters-Accepted Abstracts: J Cancer Sci Ther

Abstract :

Introduction: The standard treatment for locally advanced rectal cancer involves neoadjuvant radiochemotherapy before total mesorectal excision. However, tumor response to chemoradiation is highly variable among patients. A previous investigation that searched potential genetic markers that evaluated 128 single-nucleotide polymorphism (SNP) found significant association between superoxide dismutase 2 SNP (rs4880) and associated with radiochemotherapy resistance. The polymorphism that occurs a change of valine (V) to alaline (A) (Ala16Val-SOD2) has been associated with risk of several cancer types. The homozygous genotypes present different SOD2 efficiency causing increase in O2- levels (VV) or increase of H2O2 (AA). Cellular control of superoxide anion (O2-) and hydrogen peroxide (H2O2) concentrations is considered crucial to the cell because at low concentrations ROS can work as intracellular signal molecule related to homeostatic regulation, whilst at high levels they can cause cellular dysfunction and senescence. Objetive: Therefore, we evaluated here if an in vitro superoxide-hydrogen peroxide (S-HP) imbalance could to influence the response of colorectal cancer cell (HT-29) resistant to oxaliplatin. Methods: HT-29 cells (ATCC) were cultured in standard conditions and exposed to different concentrations of methylviologen that is a superoxide anion donators as well as porfirin that is a SOD2-like molecule, with and without oxaliplatin. The effect on viability, cell proliferation and cell cycle were evaluated by MTT assay and analysis of apoptosis by annexin V quantification using flow cytometry analysis as well as by apoptosis pathway genes modulation (p53, Bax/Bcl-2 genes ratio, caspases 8 and 3) by qRT-PCR analysis were determined. Results: The results showed that S-HP imbalance was able to increase cell cytotoxicity and apoptosis induction independent of oxaliplatin treatment. The results corroborate the potencial pharmacogenetic relevance of this polymorphism on colorectal cancer treatment.

Biography :

Email: alencarkolinski@yahoo.com.br