Action of propolis combined to docetaxel on breast tumor cells and human monocytes

Author(s)

Eliza de Oliveira Cardoso

• Document type: Doctoral Thesis
• Press: Botucatu. 2021-04-19.
• Institution: Universidade Estadual Paulista (Unesp). Instituto de Biociências. Botucatu
• Defense date: 2021-04-01
• Advisor: José Maurício Sforcin; Karina Basso Santiago

Abstract

Cancer widely affects the world population, with millions of deaths registered anually. Docetaxel (DTX) is one of the therapeutic approaches against breast cancer. Nevertheless, chemotherapy may exert side effects like toxicity and immunosuppression, leading to infections. In an attempt to reduce the adverse effects caused by chemotherapy, the dual application of medicines and natural products has been investigated. Propolis is made by honeybees showing many pharmacological properties. In this study, we investigated the cytotoxic and immunomodulatory effects of the ethanolic extract of propolis (EEP) in combination with DTX on breast cancer MCF-7 cells and on monocytes from healthy female blood donors. The cytotoxic potential of EEP+DTX was assessed by MTT assay and the type of tumor cell death (apoptosis/necrosis) was evaluated by flow cytometry. The effects of EEP, DTX and their combination on the migration and invasion of MCF-7 cells were observed. Cytokine production (IL-1β, TNF-α, IL-6 and IL-10) by monocytes was assessed by ELISA; the expression of cell surface markers (HLA-DR, CD80, TLR-2 and TLR-4) was verified by flow cytometry. We also investigated the fungicidal activity of monocytes against Candida albicans and reactive oxygen species (ROS) generation. Finally, the impact of the supernatants of treated monocytes in the viability, migration and invasiveness of tumor cells was assessed. EEP (25 μg/mL) + DTX (10 nM) enhanced the cytotoxic action of DTX alone against MCF-7 cells by inducing necrosis and inhibiting their migratory ability. EEP+DTX exerted no cytotoxic action in monocytes and stimulated HLA-DR expression, TNF-α and IL-6 production, exerted an immunorestorative action in the fungicidal activity and reduced the oxidative stress of monocytes. Data indicated that EEP in combination with lower concentrations of DTX affected the viability and migration of MCF-7 cells in vitro, and improved some immunological parameters related to monocyte functions. This is a new and relevant finding that deserves further investigation due to its practical implications, proposing a new therapeutic approach for oncologic patients in Complementary and Alternative Medicine (AU)

• FAPESP's process: 16/09986-4 - The action of propolis in combination with tamoxifen on breast cancer cells and on human monocytes: a new therapeutic approach?
• Grantee: Eliza de Oliveira Cardoso
• Support Opportunities: Scholarships in Brazil - Doctorate