Rosehip (Rosa canina) extracts prevent AKT and MAPK‐mediated cell proliferation in triple negative breast cancer cells

Abstract

Triple Negative Breast Cancer (TNBC) is an aggressive form of breast cancer, characterized by its lack of the human epidermal growth factor receptor‐2, the estrogen receptor, and the progesterone receptor. AKT and MAPK have been shown to promote cell proliferation and migration in triple negative breast cancer. Currently, the existing targeted therapy is of minimal benefit in TNBCs. Furthermore, adverse side effects and the emergence of drug‐resistant cancer cells are of great concern. Natural products have received growing interest in recent years as an alternative medicine with potential anti‐oncogenic properties. Rosehip extracts have been used as dietary supplements to relieve symptoms associated with gastrointestinal disorders and arthritis, and in our laboratory it has been shown to prevent cell proliferation in glioblastomas. This study investigated the efficacy of rosehip extracts in preventing proliferation of a triple negative breast cancer cell line (HCC1395). HCC1395 cells treated with rosehip extracts (1mg/mL–25ng/mL) demonstrated a significant decrease in cell proliferation. The observed decrease in cell proliferation was equal to or better than the decrease of cell proliferation observed when inhibitors of the MAPK (U0126, 10 μM) or AKT (LY294002, 20 μM) signaling pathways were utilized. Additionally, pretreatment of this cell line with rosehip extracts selectively decreased AKT, p70S6K, and MAPK phosphorylation suggesting these extracts prevent TNBC cell proliferation and migration by blocking the AKT and MAPK signaling mechanisms. Western blot analysis and apoptosis studies demonstrate that rosehip extracts inhibit cell proliferation without promoting apoptosis, but induce cell cycle arrest.To investigate the potential clinical application of rosehip extracts we examined whether rosehip extracts could enhance the chemotherapeutic properties of Doxorubicin (20μM), a chemotherapeutic agent used to treat breast cancer. Rosehip extracts demonstrated a greater anti‐proliferative effect than Doxorubicin alone and is equally effective in combination with Doxorubicin. These data suggest that rosehip extracts are capable of decreasing cell proliferation in a triple negative breast cancer cell line by blocking the AKT and MAPK signaling pathways and by regulating the cell cycle. Moreover, rosehip extracts demonstrate a greater inhibition of cell proliferation, when given alone and combination with Doxorubicin. This investigation demonstrates that rosehip extracts may serve as either an alternative or complimentary treatment to current chemotherapeutic regimens for triple negative breast cancer.Support or Funding InformationNational Science Foundation Graduate Research Fellowship Program Grant No. (NSF 13‐085)