Possible cytotoxic and immunomodulatory action of geopropolis associated with doxorrubicin on human monocytes

Author(s)

Lucas Pires Garcia Oliveira

• Document type: Master's Dissertation
• Press: Botucatu. 2018-08-22.
• Institution: Universidade Estadual Paulista (Unesp). Instituto de Biociências. Botucatu
• Defense date: 2018-02-28
• Advisor: José Mauricio Sforcin; Bruno José Conti

Abstract

Cancer is a disease that strikes people on many continents, resulting in millions of deaths annually. The antineoplastic treatments are known for their wide range of side effects such as toxicity, induction of resistance in tumor cells, lack of selectivity between normal and tumor cells, as well as immunosuppression with consequent onset of infections. In order to mitigate the side effects caused by antitumor agents, the administration of natural products concomitantly with drugs has been investigated. The present work was designed to elucidate a possible cytotoxic and immunomodulatory action of geopropolis (GEO) combined with doxorubicin (DOX) in a lower concentration on monocytes of healthy individuals. Cell viability was analyzed by the MTT method, the expression of surface markers (HLA-DR, CD80, CD40 , TLR-2, TLR-4) by flow cytometry, the production of cytokines (IL-1β, TNF-α, IL-6 and IL-10) by ELISA, gene expression by RT-PCR, protein production by western blot. The microbicidal activity of monocytes was evaluated against Candida albicans, Escherichia coli and Streptococcus mutans, as well as hydrogen peroxide production. MTT assay showed that none of the treatments exerted a cytotoxic action. Monocytes incubated with GEO and the GEO + DOX had an increased TNF-α and IL-10 production, while IL-1β and IL-6 production decreased when compared to control. An increased TLR-4 and CD80 expression was seen after incubation with the combination, whereas GEO alone increased TLR-4 expression. The combination increased the bactericidal action of monocytes against E. coli. No alterations were found in the fungicidal activity nor in the bactericidal activity against S. mutans. Gene expression of LC3 and NF-κB were decreased by all treatments, whereas phospho-ΙκBα expression was decreased by GEO but the association maintained baseline levels. Our findings indicated that the combination was not cytotoxic for monocytes and exerted an immunomodulatory action on the expression of cell surface markers and cytokine production, suggesting an activator profile of GEO + DOX. The use of this combination could reduce the concentration of DOX and the side effects caused by chemotherapy. (AU)

• FAPESP's process: 16/02249-4 - Immunotoxicologic / immunomodulatory action of geopropolis associated with doxorubicin on human monocytes
• Grantee: Lucas Pires Garcia Oliveira
• Support Opportunities: Scholarships in Brazil - Master