Abstract
Breast cancer is the most common form of cancer in the female population worldwide where approximately 30% of these women will succumb to their disease. The identification of novel, efficacious and safe anticancer drugs is thus essential to mitigate the morbidity and mortality associated with this disease. More recently, the study of anticancer properties from natural products has regained popularity as natural entities provide more biodiversity of chemical structures with biological and medicinal activity. Based on a documented library of the most common medicinal plants used by the indigenous people of North America, we have examined the anti-breast cancer properties of extracts from Juniperus communis (common juniper).
Using methanolic extracts from juniper needles and branches, we conducted bioassay-guided fractionation to assess growth inhibition of the highly malignant MB231 breast cancer cell line. The isolation and identification of active juniper constituents were performed through high performance liquid chromatography (HPLC) and standard spectroscopic analysis (1D- and 2D-nuclear magnetic resonance [NMR] and low-resolution and high-resolution mass spectrometry).
We characterized the diterpene isocupressic acid and the aryltetralin lignan deoxypodophyllotoxin as very potent inhibitors of cancer cell growth using dose-response and kinetic cell viability assays. Using a series of cellular and molecular tests, we also found that isocupressic acid and deoxypodophyllotoxin block MB231 cell cycling through the suppression of the ERK/MAPK and the NFκB signaling pathways. In addition to the blockade of the cell's survival cascade, both compounds concomitantly induced CASPASE-3-dependant apoptosis of MB231 cells within hours of treatment.
Our findings emphasize the potential and importance of natural products screening for new chemical entities with novel anticancer activities. Natural products research complemented with the wealth of information available through the ethnobotanical and ethnopharmacological knowledge of the indigenous natives will provide new candidate entities with desirable bioactivities to develop new cancer therapies.
Citation Format: Gilles A. Robichaud, Nadia Picot, Stéphanie Jean, Caitlyn Carpenter, Chris A. Gray. The characterization of anti-breast cancer compounds isolated from the Juniperus communis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2266. doi:10.1158/1538-7445.AM2013-2266