E. S. Knudsen and J. Y. Wang, “Dual Mechanisms for the Inhibition of E2F Binding to RB by Cyclin-Dependent Kinase-Mediated RB Phosphorylation,” Molecular and Cellular Biology, Vol. 17, No. 10, 1997, pp. 5771-583.

has been cited by the following article:

• TITLE: Effect of Rosehip (Rosa Canina) Extracts on Human Brain Tumor Cell Proliferation and Apoptosis

  AUTHORS: Patrice Cagle, Ombeni Idassi, Janelle Carpenter, Radiah Minor, Ipek Goktepe, Patrick Martin

  KEYWORDS: Rosehip; Rosa Canina; Glioma; Glioblastoma Multiforme; Cell Proliferation; Apoptosis; Temozolomide; MAPK; AKT

  JOURNAL NAME: Journal of Cancer Therapy, Vol.3 No.5, October 18, 2012

  ABSTRACT: Rosehips are blossoms from the wild rose (Rosa canina) and are commonly used as an herbal remedy. Previous reports have shown that extracts made from rosehip plants are able to reduce cell proliferation of cancer cells. In this study, we investigated the efficacy of rosehip extracts in preventing cell proliferation of three human glioblastoma cell lines A-172, U-251 MG and U-1242 MG cell lines. Each of the glioblastoma cell lines treated with rosehip extracts (1 mg/mL-25 ng/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 inhibitors of the MAPK (U0126, 10 μM) or AKT (LY294002, 20 μM) signaling pathways were utilized. Additionally, pretreatment of the these cell lines with Rosehip extracts (1 mg/mL-25 ng/mL) selectively decreased AKT, MAPK, and p70S6K phosphorylation suggesting these extracts prevent glioblastoma multiforme cell proliferation by blocking both the MAPK and AKT signaling mechanisms. Results from colorimetric cell death assays, cell cycle analysis by flow cytometry, as well as western blot studies demonstrate that rosehip extracts inhibit cell proliferation but do not promote apoptosis. Moreover, rosehip extracts were able to increase the efficacy of Temozolomide, a chemotherapeutic agent used to treat patients with glioblastomas. Surprisingly, rosehip extracts demonstrated a greater inhibition of cell proliferation than in combination with Temozolomide (100 μM) or Temozolomide as a single agent. Taken together these data suggest that rosehip extracts are capable of decreasing glioblastoma cell proliferation without promoting apoptosis and demonstrate a greater cell proliferation inhibitory effect than Temozolomide. More importantly, rosehip extracts may serve as an alternative or compliment to current chemotherapeutic regimens for glioblastomas.