Triple Negative Breast Cancer (TNBC) is an aggressive form of breast cancer, characterized by its lack of the human epidermal growth factor receptor-2 (HER-2), the estrogen receptor (ER), and the progesterone receptor (PR). The high prevalence of triple negative tumors in young women is more commonly observed in young African American (AA) women. Currently, the existing targeted therapy is of minimal benefit in TNBCs. Akt and MAPK have been shown to promote cell proliferation in triple negative breast cancer and MAPK expression may be an underlying mechanism contributing to the generation of chemo-resistance in triple-negative breast cancer. Due to major concerns involving the occurrence of side effects and the emergence of drug-resistant cancer cells, there has been growing interest in the use of naturally occurring molecules with chemo-preventive and chemo- therapeutic properties in cancer treatment. Rosehip extracts have been used as dietary supplements to relieve symptoms associated with diarrhea, gastritis, and rheumatoid arthritis and have been shown to prevent cell proliferation in glioblastomas. This study investigated the efficacy of rosehip extracts in preventing cell proliferation in African American triple negative (HCC70, HCC1806) and luminal (HCC1500) breast cancer cell lines. Each of the breast cancer cell lines were treated with rosehip extracts (1mg/mL -25ng/mL) demonstrated a significant decrease in cell proliferation. The rosehip extract-mediated decrease in cell proliferation was equal to or better than the decrease of cell proliferation observed when known inhibitors of the MAPK (U0126, 10 μM) or AKT (LY294002, 20 μM) signaling pathways were utilized. Additionally, pretreatment of these cell lines with these Rosehip extracts (1mg/mL -25ng/mL) selectively decreased AKT, MAPK, p70S6K, and S6 phosphorylation suggesting these extracts prevent AA TNBC cell proliferation by blocking both the MAPK and AKT signaling mechanisms. Results from cell cycle analysis by flow cytometry, western blot analysis, as well as apoptosis studies demonstrate that rosehip extracts inhibit cell proliferation but do not promote apoptosis. Rosehip extracts also have a synergistic effect with Doxorubicin (20µM), a chemotherapeutic agent used to treat patients with breast cancer, in preventing triple negative breast cancer cell proliferation. Taken together these data suggest that rosehip extracts are capable of decreasing cell proliferation in African American triple negative breast cancer cells without promoting apoptosis and demonstrate a synergistic inhibition of cell proliferation with Doxorubicin, and rosehip extracts may serve as an alternative or compliment to current chemotherapeutic regimens for triple negative breast cancer.

Citation Format: Patrice Cagle, Tonisha Coburn, Patrick M. Martin. Rosehip (Rosa canina) extracts prevent MAPK and AKT-mediated cell proliferation in African American triple-negative breast cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3213. doi:10.1158/1538-7445.AM2014-3213