Positive effects of antitumor drugs in combination with propolis on canine osteosarcoma cells (spOS-2) and mesenchymal stem cells

Abstract

The combination of lower concentrations of antitumor drugs (carboplatin - CARB, doxorubicin - DOX, and methotrexate - MET) with propolis was investigated against canine osteosarcoma (spOS-2) and mesenchymal stem cells (MSC) in vitro. The mechanism of action in the combinations was analyzed. spOS-2 cells were incubated up to 72 h with propolis (50 μg/ml) alone or in combination with CARB (10-400 μmol/l), DOX (0.5-2 μmol/l) or MET (50-200 μmol/l). Cell viability was assessed by MTT assay, apoptosis/necrosis by flow cytometry, and MSC was incubated with the optimum combination. Propolis alone exerted no cytotoxic action against spOS-2 cells, whereas CARB (400, 200 and 100 μmol/l) exhibited the highest cytotoxic effects comparing to DOX and MET. The combination of propolis with the lowest concentrations of CARB led to better results comparing to CARB alone, which was not observed using DOX and MET. Apoptosis was involved in the action of propolis + CARB in spOS-2 cells. MSC were not affected by CARB/propolis, indicating that the cytotoxic action of the combination was specific to tumor cells but not to normal ones. Propolis improved the action of CARB against spOS-2 cells using lower concentrations of this drug, without affecting MSC. These findings are relevant and indicate a possible application of propolis in OSA treatment.

Brazilian green propolis: A novel tool to improve the cytotoxic and immunomodulatory action of docetaxel on MCF‐7 breast cancer cells and on women monocyte

“…Propolis made by Africanized honeybees enhanced the cytotoxic effect of carboplatin against canine osteosarcoma cells (Bernardino et al, 2018). In our study, EEP improved DTX cytotoxic effects against MCF-7 cells.…”

“…Brazilian green propolis exerted a cytotoxic activity against lung cancer A549 cells and laryngeal epidermoid carcinoma HEp-2 cells by inducing apoptosis (Fri on-Herrera, Díaz-García, Ruiz-Fuentes, Rodríguez-Sánchez, & Sforcin, 2015;Silva, Fri on-Herrera, Bartolomeu, Gorgulho, & Sforcin, 2017). This ethanol solution extract of propolis (EEP) also enhanced the action of an antitumor agent (carboplatin) against canine osteosarcoma in vitro (Bernardino, Bersano, Lima Neto, & Sforcin, 2018). In addition, EEP displayed an immunomodulatory action in monocytes and dendritic cells, stimulating the initial steps of the immune response (Búfalo, Bordon-Graciani, Conti, Golim, & Sforcin, 2014;Conti et al, 2016;.…”

Evaluation of the Effect of Five Colombian Propolis Extracts on the Expression of Genes Associated with Cell Cycle and Inflammation in a Canine Osteosarcoma Cell Line

“…[40] There is no information available on the ethnopharmacological activity of Colombian propolis associated with the antitumor effect, except for our own previous reports in which it was shown that EEP induced early and late apoptosis, related to the alteration of mitochondrial membrane potential, likewise, a significant decrease in the invasion, in canine osteosarcoma cells. [41,42] In the first place, the characterization consisted in evaluating proliferation, the exponential phase was established between 72 and 96 hr, a period of time in which the cell confluence was close to 70%, which could suggest that contact stimulates cell growth. These results coincide with tests carried out in the characterization of primary culture fibroblasts cultured with 10% SFB by other authors.…”

Comparison of Biochemical, Antimicrobial and Cytotoxic Activities of Different Propolis Samples from Malatya and Bilecik

“…We found that all propolises have less cytotoxic effect BEAS2B cell line than A549 cell line showed in Tablo 4. It is tested that the combination of lower concentrations of antitumor drugs (carboplatin -CARB, doxorubicin -DOX, and methotrexate -MET) with propolis was investigated against canine osteosarcoma (spOS-2) and mesenchymal stem cells (MSC) in vitro [29]. They found that propolis alone exerted no cytotoxic action against spOS-2 cells, whereas CARB (400, 200 and 100 μmol/l) exhibited the highest cytotoxic effects comparing to DOX and MET.…”