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eCAM Advance Access published online on April 11, 2006

eCAM, doi:10.1093/ecam/nel015
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© The Author (2006). Published by Oxford University Press. All rights reserved.
Received October 19, 2005
Accepted March 16, 2006

Original Article

Insulin-sensitizing and Anti-proliferative Effects of Argania spinosa Seed Extracts

Samira Samane 1, Josette Noël 2, Zoubida Charrouf 3, Hamid Amarouch 4, and Pierre Selim Haddad 5 *

1 Groupe d'étude des protéines membranaires, Université Laval, Québec, Canada; Department of Pharmacology, Université Laval, Québec, Canada; Institute of Functional Foods and Nutraceuticals, Université Laval, Québec, Canada; Department of Biology, Université Hassan II, Casablanca, Morocco
2 Groupe d'étude des protéines membranaires, Université Laval, Québec, Canada; Department of Physiology, Université de Montréal, Montréal, Canada
3 Department of Chemistry, Université Mohammed V, Rabat, Morocco
4 Department of Biology, Université Hassan II, Casablanca, Morocco
5 Groupe d'étude des protéines membranaires, Université de Montréal, Montréal, Canada; Department of Pharmacology, Université de Montréal, Montréal, Canada; Department of Physiology, Université de Montréal, Montréal, Canada; Institute of Functional Foods and Nutraceuticals, Université Laval, Québec, Canada

* To whom correspondence should be addressed.
Pierre Selim Haddad, E-mail: pierre.haddad{at}umontreal.ca


   Abstract

Argania spinosa is an evergreen tree endemic of southwestern Morocco. Many preparations have been used in traditional Moroccan medicine for centuries to treat several illnesses including diabetes. However, scientific evidence supporting these actions is lacking. Therefore, we prepared various extracts of the argan fruit, namely keel, cake and argan oil extracts, which we tested in the HTC hepatoma cell line for their potential to affect cellular insulin responses. Cell viability was measured by Trypan Blue exclusion and the response to insulin evaluated by the activation of the extracellular regulated kinase (ERK1/2), ERK kinase (MEK1/2) and protein kinase B (PKB/Akt) signaling components. None of the extracts demonstrated significant cytotoxic activity. Certain extracts demonstrated a bi-phasic effect on ERK1/2 activation; low doses of the extract slightly increased ERK1/2 activation in response to insulin, whereas higher doses completely abolished the response. In contrast, none of the extracts had any significant effect on MEK whereas only a cake saponin subfraction enhanced insulin-induced PKB/Akt activation. The specific action of argan oil extracts on ERK1/2 activation made us consider an anti-proliferative action. We have thus tested other transformed cell lines (HT-1080 and MSV-MDCK-INV cells) and found similar results. Inhibition of ERK1/2 activation was also associated with decreased DNA synthesis as evidenced by [3H]thymidine incorporation experiments. These results suggest that the products of Argania spinosa may provide a new therapeutic avenue against proliferative diseases.

Keywords: cancer; diabetes; MAPK; PKB; transformed cell lines.
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