Rapamycin and fructose-1,6-bisphosphate reduce the HEPG2 cell proliferation via increase of free radicals and apoptosis

da Silva,Elisa Feller Gonçalves; Krause,Gabriele Catyana; Lima,Kelly Goulart; Haute,Gabriela Viegas; Pedrazza,Leonardo; Mesquita,Fernanda Cristina; Basso,Bruno Souza; Velasquez,Anderson Catarina; Nunes,Fernanda Bordignon; de Oliveira,Jarbas Rodrigues

doi:10.3892/or.2016.5111

Rapamycin and fructose-1,6-bisphosphate reduce the HEPG2 cell proliferation via increase of free radicals and apoptosis

Authors:
- Elisa Feller Gonçalves da Silva
- Gabriele Catyana Krause
- Kelly Goulart Lima
- Gabriela Viegas Haute
- Leonardo Pedrazza
- Fernanda Cristina Mesquita
- Bruno Souza Basso
- Anderson Catarina Velasquez
- Fernanda Bordignon Nunes
- Jarbas Rodrigues de Oliveira
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Affiliations: Laboratory of Cellular Biophysics and Inflammation, Department of Cellular and Molecular Biology, School of Biosciences, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Rio Grande do Sul, CEP 90619‑900, Brazil
Published online on: September 20, 2016 https://doi.org/10.3892/or.2016.5111
Pages: 2647-2652

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Abstract

Hepatocellular carcinoma is the most prevalent type of tumor among primary tumors affecting the liver. Rapamycin is currently used as a basis for chemotherapy in the treatment of cancers, including the liver. Because it shows several adverse effects, minimizing these effects without compromising efficacy is important. In this sense other drugs may be used concomitantly. One of these drugs is fructose-1,6-bisphosphate (FBP), which has shown therapeutic effect in various pathological situations, having antioxidant and anti-inflammatory proprieties. The objective of the present study was to evaluate the activity of rapamycin in combination with the FBP in HepG2 cell proliferation and the mechanisms involved. HepG2 cells were analyzed after 72 h of treatment with both drugs. Cell proliferation, cytotoxicity, cytokines, apoptosis, senescence, autophagy and oxidative stress were accessed. Ιt was demonstrated that the combination is more efficient than the single use of substances, because subtherapeutic doses of rapamycin, when associated to FBP become effective, reducing cell proliferation, through a significant increase in the production of tiobarbituric acid reactive substances (TBARS), suggesting that this might be the cause of death by apoptosis. According to these results, we believe that the association of both drugs may be a promising choice for the treatment of hepatocarcinoma.

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