Cannabidiol Kills Cancer

[Ironjustic]

5-Lipoxygenase and anandamide hydrolase (FAAH) mediate the
antitumor activity of cannabidiol, a non-psychoactive
cannabinoid Authors: Massi, P.1; Valenti, M.2; Vaccani, A.2;
Gasperi, V.3; Perletti, G.2; Marras, E.2; Fezza, F.;
Maccarrone, M.; Parolaro, D.2

Source: Journal of Neurochemistry, Volume 104, Number 4,
February 2008 , pp. 1091-1100(10)

Publisher: Blackwell Publishing Abstract:

It has been recently reported that cannabidiol (CBD), a non-
psychoactive cannabinoid, is able to kill glioma cells, both
in vivo and in vitro, independently of cannabinoid receptor
stimulation. However, the underlying biochemical mechanisms
were not clarified. In the present study, we performed
biochemical analysis of the effect of CBD both in vivo, by
using glioma tumor tissues excised from nude mice, and in
vitro, by using U87 glioma cells. In vivo exposure of tumor
tissues to CBD significantly decreased the activity and
content of 5-lipoxygenase (LOX, by =E2=88=BC=E2=80=8940%),
and = of its end product leukotriene B4
(=E2=88=BC=E2=80=8925%). In contrast cyclooxygenase (COX)-2
activity and content, and the amount of its end product
prostaglandin E2, were not affected by CBD. In addition, in
vivo treatment with CBD markedly stimulated
(=E2=88=BC=E2=80=
=89175%)
the activity of fatty acid amide hydrolase (FAAH), the main
anandamide- degrading enzyme, while decreasing anandamide
content (=E2=88=BC=E2=80=8930%= ) and binding to CB1
cannabinoid receptors (=E2=88=BC=E2=80=8925%). In vitro pre-t=
reatment of U87 glioma cells with MK-886, a specific 5-LOX
inhibitor, significantly enhanced the antimitotic effect of
CBD, whereas the pre- treatment with indomethacin (pan-COX
inhibitor) or celecoxib (COX-2 inhibitor), did not alter CBD
effect. The study of the endocannabinoid system revealed that
CBD was able to induce a concentration-dependent increase of
FAAH activity in U87 cells. Moreover, a significantly reduced
growth rate was observed in FAAH-over-expressing U87 cells,
compared to wild-type controls. In conclusion, the present
investigation indicates that CBD exerts its antitumoral
effects through modulation of the LOX pathway and of the
endocannabinoid system, suggesting a possible interaction of
these routes in the control of tumor growth. Keywords:
cannabidiol; cyclooxygenase; endocannabinoid system; glioma;
lipoxygenase

Document Type: Research article

DOI: 10.1111/j.1471-4159.2007.05073.x

Affiliations: 1: Department of Pharmacology, Chemotherapy and
Toxicology, University of Milan, Milan, Italy 2: Department of
Structural and Functional Biology, Pharmacology Section,
Center of Neuroscience, University of Insubria, Busto Arsizio,
Italy 3: Department of Biomedical Sciences, University of
Teramo, Teramo, Italy

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Man Is A Herbivore! http://tinyurl.com/a3cc3

DEAD PEOPLE WALKING http://tinyurl.com/zk9fk

[Ironjustic]

On Mar 12, 11:49=C2=A0am, "ironjust...@aol.com"
<ironjust...@aol.com> wrote:exerts its antitumoral effects
through modulation of the LOX pathway <<

Effect of catechol derivatives on cell growth and
lipoxygenase activity

Julie Simpson, Rebecca Forrester, Michael J. Tisdale, David
C. Billington=E2=80=A0 and Daniel L. Rathbone, School of Life
and Health Sciences, Aston University, Birmingham B4 7ET, UK
Received 28 February 2003; revised 1 May 2003; accepted 22
May 2003. ; Available online 24 June 2003. Abstract
Derivatives of salicylic acid have been synthesized as
potential lipoxygenase inhibitors. Agents containing a
phenolic dihydroxy moiety showed potent (IC5010=E2=88=92=
6=E2=80=93 10=E2=88=927 M) inhibition of the growth of murine
colonic tumour cells in vitro, and were effective inhibitors
of 5-, 12- and 15-lipoxygenase in intact cells. The catechols
were also potent inhibitors of rabbit reticulocyte 15-
lipoxygenase (IC50 1 =CE=BCM). Potent (IC50
10=E2=88=926=E2=80=9310=E2=88=927 M) inhibition of the growth
o= f murine colonic tumour cells in vitro was observed along
with inhibition of 5-, 12- and 15-lipoxygenase in intact
cells and inhibition of rabbit reticulocyte 15- lipoxygenase
(IC50 1 =CE=BCM).

Corresponding author. Tel.: +44-121-359-3611; fax:
+44-121-359-0572

=E2=80=A0 Present address: L'Or=C3=A9al Recherche,
Recherche Avanc=C3=A9e Sc= iences de la Mati=C3=A8re, 1,
Avenue Eug=C3=A8ne Schueller, BP 22, Aulnay sous Bois,
Cede= x, France.

Bioorganic & Medicinal Chemistry Letters Volume 13, Issue 15,
4 August 2003, Pages 2435-2439 Dedicated to Professor David
Crout to mark the occastion of his retirement.

doi:10.1016/S0960-894X(03)00528-6 Copyright =C2=A9 2003
Elsevier Ltd. All rights reserved.

-------------------------------

Lipoxygenases (LOXs) are nonheme iron-containing enzymes.

http://circres.ahajournals.org/cgi/content/abstract/94/12/1527

--------------------------------------------
http://www.nature.com/cdd/journal/v8/n8/full/4400908a.html

Lipoxygenases and their involvement in programmed cell death

M Maccarrone, G Melino and A Finazzi-Agro

Department of Experimental Medicine and Biochemical Sciences,
University of Rome Tor Vergata, I-00133 Rome, Italy
Correspondence to: M MaccarroneA Finazzi-Agro, Department of
Experimental Medicine and Biochemical Sciences, University of
Rome Tor Vergata, Via di Tor Vergata 135, I-00133 Rome, Italy.
Tel: +39 06 72596468; Fax: +39 06 72596468; E-mail:
Finazzi@uniroma2.it or Maccarrone@med.uniroma2.it

Edited by H Ichijo Abstract

Lipoxygenases are a family of enzymes which dioxygenate
unsaturated fatty acids, thus initiating lipoperoxidation of
membranes and the synthesis of signaling molecules.
Consequently, they induce structural and metabolic changes in
the cell in a number of pathophysiological conditions.
Recently, a pro-apoptotic effect of lipoxygenase, and of the
hydroperoxides produced thereof, has been reported in
different cells and tissues, leading to cell death.
Anti-apoptotic effects of lipoxygenases have also been
reported; however, this has often been based on the use of
enzyme inhibitors. Here we review the characteristics of the
lipoxygenase family and its involvement in the initiation of
oxidative stress-induced apoptosis. Finally, we discuss the
role of lipoxygenase activation in apoptosis of animal and
plant cells, suggesting a common signal transduction pathway
in cell death conserved through evolution of both kingdoms.
Cell Death and Differentiation (2001) 8, 776-784

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Jesus Was A Vegetarian! http://jesuswasavegetarian.7h.com

Man Is A Herbivore! http://tinyurl.com/a3cc3

DEAD PEOPLE WALKING http://tinyurl.com/zk9fk

> 5-Lipoxygenase and anandamide hydrolase (FAAH) mediate the
> antitumor activity of cannabidiol, a non-psychoactive
> cannabinoid Authors: Massi, P.1; Valenti, M.2; Vaccani, A.2;
> Gasperi, V.3; Perletti, G.2; Marras, E.2; Fezza, F.;
> Maccarrone, M.; Parolaro, D.2
>
> Source: Journal of Neurochemistry, Volume 104, Number 4,
> February 2008 , pp. 1091-1100(10)
>
> Publisher: Blackwell Publishing Abstract:
>
> It has been recently reported that cannabidiol (CBD), a non-
> psychoactive cannabinoid, is able to kill glioma cells, both
> in vivo and in vitro, independently of cannabinoid
> receptor stimulation. However, the underlying biochemical
> mechanisms were not clarified. In the present study, we
> performed biochemical analysis of the effect of CBD both
> in vivo, by using glioma tumor tissues excised from nude
> mice, and in vitro, by using U87 glioma cells. In vivo
> exposure of tumor tissues to CBD significantly decreased
> the activity and content of 5-lipoxygenase (LOX, by
> =E2=88=BC=E2=80=8940%), an=
d of its end
> product leukotriene B4 (=E2=88=BC=E2=80=8925%). In contrast
> cyclooxygenase (COX)-2 activity and content, and the amount
> of its end product prostaglandin E2, were not affected by
> CBD. In addition, in vivo treatment with CBD markedly
> stimulated (=E2=88=BC=E2=
=80=89175%)
> the activity of fatty acid amide hydrolase (FAAH), the main
> anandamide- degrading enzyme, while decreasing anandamide
> content (=E2=88=BC=E2=80=893=
%) and
> binding to CB1 cannabinoid receptors
> (=E2=88=BC=E2=80=8925%). In vitro pre=
-treatment
> of U87 glioma cells with MK-886, a specific 5-LOX inhibitor,
> significantly enhanced the antimitotic effect of CBD,
> whereas the pre- treatment with indomethacin (pan-COX
> inhibitor) or celecoxib (COX-2 inhibitor), did not alter CBD
> effect. The study of the endocannabinoid system revealed
> that CBD was able to induce a concentration-dependent
> increase of FAAH activity in U87 cells. Moreover, a
> significantly reduced growth rate was observed in
> FAAH-over-expressing U87 cells, compared to wild-type
> controls. In conclusion, the present investigation indicates
> that CBD exerts its antitumoral effects through modulation
> of the LOX pathway and of the endocannabinoid system,
> suggesting a possible interaction of these routes in the
> control of tumor growth. Keywords: cannabidiol;
> cyclooxygenase; endocannabinoid system; glioma; lipoxygenase
>
> Document Type: Research article
>
> DOI: 10.1111/j.1471-4159.2007.05073.x
>
> Affiliations: 1: Department of Pharmacology, Chemotherapy
> and Toxicology, University of Milan, Milan, Italy 2:
> Department of Structural and Functional Biology,
> Pharmacology Section, Center of Neuroscience, University of
> Insubria, Busto Arsizio, Italy 3: Department of Biomedical
> Sciences, University of Teramo, Teramo, Italy
>
> Who loves ya. Tom
>
> Jesus Was A Vegetarian!http://jesuswasavegetarian.7h.com
>
> Man Is A Herbivore!http://tinyurl.com/a3cc3
>
> DEAD PEOPLE WALKINGhttp://tinyurl.com/zk9fk