Tea tree oil presents in vitro antitumor activity on breast cancer cells without cytotoxic effects on fibroblasts and on peripheral blood mononuclear cells

The purpose of this study was to investigate some possible mechanisms underlying the in vitro antitumor activity of tea tree oil (TTO) on human and mouse breast cancer cells (MCF-7 and 4T1, respectively) and its cytotoxicity on fibroblasts (HFF-1) and on peripheral blood mononuclear cells (PBMCs). TTO High-Resolution Gas Chromatography (HRGC) showed seventeen main constituents, such as Terpinen-4-ol, γ-Terpinene, and α-Terpinene. High TTO concentrations (≥ 600 μg/mL) showed a remarkable antitumor activity, decreasing cell viability and cell proliferation of MCF-7 and 4T1 cells. TTO at 300 μg/mL increased the number of MCF-7 cells in the early stages of apoptosis and increased the BAX/BCL-2 genes ratio. TTO, mainly at 300 μg/mL, decreased cell growth and arrested MCF-7 cells in the S phase of the cell cycle. Lower antitumor concentrations (≤300 μg/mL) evaluated in MCF-7 and 4T1 cells were not cytotoxic to PBMCs and HFF-1. Also, TTO (300 μg/mL) was able to induce cell proliferation in fibroblasts after 72 h, indicating non-cytotoxic effect in these cells. TTO exhibited in vitro antitumor effect on MCF-7 and 4T1 cells by decreasing cell viability and modulating apoptotic pathways and cell cycle arrestment of MCF-7 cells. In this sense, our study provides new perspectives on the potential use of TTO for the development of new alternative therapies to treat topically locally advanced breast cancer (LABC).