Cannabinoids: A New Hope For Breast Cancer Therapy?

Cancer Treatment Reviews 38 (2012) 911–918

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Cancer Treatment Reviews
journal homepage: www.elsevierhealth.com/journals/ctrv

New Drugs

Cannabinoids: A new hope for breast cancer therapy?
María M. Caffarel a, Clara Andradas, Eduardo Pérez-Gómez, Manuel Guzmán, Cristina Sánchez ⇑
Dept. Biochemistry and Molecular Biology I, School ofBiology, Complutense University-CIBERNED-IRYCIS, Madrid, Spain

a r t i c l e

i n f o

a b s t r a c t
Breast cancer is a very common disease that affects approximately 1 in 10 women at some point in their lives. Importantly, breast cancer cannot be considered a single disease as it is characterized by distinct pathological and molecular subtypes that are treated with different therapies andhave diverse clinical outcomes. Although some highly successful treatments have been developed, certain breast tumors are resistant to conventional therapies and a considerable number of them relapse. Therefore, new strategies are urgently needed, and the challenge for the future will most likely be the development of individualized therapies that specifically target each patient’s tumor.Experimental evidence accumulated during the last decade supports that cannabinoids, the active components of Cannabis sativa and their derivatives, possess anticancer activity. Thus, these compounds exert anti-proliferative, pro-apoptotic, antimigratory and anti-invasive actions in a wide spectrum of cancer cells in culture. Moreover, tumor growth, angiogenesis and metastasis are hampered by cannabinoidsin xenograft-based and genetically-engineered mouse models of cancer. This review summarizes our current knowledge on the antitumor potential of cannabinoids in breast cancer, which suggests that cannabinoid-based medicines may be useful for the treatment of most breast tumor subtypes. Ó 2012 Elsevier Ltd. All rights reserved.

Article history: Received 16 May 2012 Received in revised form 11June 2012 Accepted 17 June 2012

Keywords: Cannabinoids G protein-coupled receptors Preclinical studies

Introduction Cannabinoids are a family of unique compounds synthesized by Cannabis sativa (marijuana) that have not been found as yet in any other plant. The main representative cannabinoid, owing to its high abundance in the plant and its strong biological activity, isD9-tetrahydrocannabinol (THC).1 For decades, and mainly due to their lipophilic nature, it was assumed that cannabinoids exerted their effects by perturbing the biophysical properties of biological membranes.2 This scenario changed dramatically in 1990, when the first cannabinoid-specific membrane receptor (CB1) was characterized and cloned.3 This discovery boosted the scientific research on cannabinoids, which currentlyconstitutes a very active field in biomedicine. The term cannabinoid includes now not only the marijuana-derived compounds that are structurally related to THC (phytocannabinoids), but also the synthetic molecules that activate the same primary targets as THC (synthetic cannabinoids) and a family of endogenously produced compounds that engage cannabinoid receptors (endocannabinoids), of whichanandamide (arachidonoylethanolamide, AEA)4 and 2-arachidonoylglicerol (2-AG)5,6 are the main – if not only – representatives. Two G
⇑ Corresponding author. Address: Dept. Biochemistry and Molecular Biology I, School of Biology, Complutense University, C/ José Antonio Novais, 2, 28040 Madrid, Spain. Tel.: +34 913944668; fax: +34 913944672. E-mail address: cristina.sanchez@quim.ucm.es (C. Sánchez). aPresent address: Dept. Pathology, University of Cambridge, Cambridge, UK.
0305-7372/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ctrv.2012.06.005

protein-coupled receptors (GPCRs) that are selectively engaged by cannabinoids have been cloned so far (CB1 and CB2),3,7 and some evidence indicates that cannabinoids may act by binding to additional...