Cannabinoid action induces autophagy (kills cancer cells)

[G_j]

http://www.jci.org/articles/view/37948

J. Clin. Invest. doi:10.1172/JCI37948.
Copyright © 2009, The American Society for Clinical Investigation
Research Article

Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma cells

María Salazar1,2, Arkaitz Carracedo1, Íñigo J. Salanueva1, Sonia Hernández-Tiedra1, Mar Lorente1,2, Ainara Egia1, Patricia Vázquez3, Cristina Blázquez1,2, Sofía Torres1, Stephane García4, Jonathan Nowak4, Gian María Fimia5, Mauro Piacentini5, Francesco Cecconi6, Pier Paolo Pandolfi7, Luis González-Feria8, Juan L. Iovanna4, Manuel Guzmán1,2, Patricia Boya3 and Guillermo Velasco1,2

1Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, Madrid, Spain.
2Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
33D Lab (Development, Differentiation, and Degeneration), Department of Cellular and Molecular Physiopathology, Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain.
4INSERM U624, Campus de Luminy, Marseille, France.
5National Institute for Infectious Diseases, IRCCS “L. Spallanzani,” Rome, Italy.
6Laboratory of Molecular Neuroembryology, IRCCS Fondazione Santa Lucia and Department of Biology, University of Rome “Tor Vergata,” Rome, Italy.
7Cancer Genetics Program, Beth Israel Deaconess Cancer Center and Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
8Department of Neurosurgery, University Hospital, Tenerife, Spain.

Address correspondence to: Guillermo Velasco, Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, c/ José Antonio Novais s/n, 28040 Madrid, Spain. Phone: [phone]; Fax: [phone]; E-mail: [e-mail].

Published April 1, 2009
Received for publication November 3, 2008, and accepted in revised form February 11, 2009.

Autophagy can promote cell survival or cell death, but the molecular basis underlying its dual role in cancer remains obscure. Here we demonstrate that ?9-tetrahydrocannabinol (THC), the main active component of marijuana, induces human glioma cell death through stimulation of autophagy. Our data indicate that THC induced ceramide accumulation and eukaryotic translation initiation factor 2? (eIF2?) phosphorylation and thereby activated an ER stress response that promoted autophagy via tribbles homolog 3–dependent (TRB3-dependent) inhibition of the Akt/mammalian target of rapamycin complex 1 (mTORC1) axis. We also showed that autophagy is upstream of apoptosis in cannabinoid-induced human and mouse cancer cell death and that activation of this pathway was necessary for the antitumor action of cannabinoids in vivo. These findings describe a mechanism by which THC can promote the autophagic death of human and mouse cancer cells and provide evidence that cannabinoid administration may be an effective therapeutic strategy for targeting human cancers.


..more..
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http://www.sciencedaily.com/releases/2009/04/090401181217.htm

Active Component Of Marijuana Has Anti-cancer Effects, Study Suggests

ScienceDaily (Apr. 9, 2009) — Guillermo Velasco and colleagues, at Complutense University, Spain, have provided evidence that suggests that cannabinoids such as the main active component of marijuana (THC) have anticancer effects on human brain cancer cells.

In the study, THC was found to induce the death of various human brain cancer cell lines and primary cultured human brain cancer cells by a process known as autophagy.

Consistent with the in vitro data, administration of THC to mice with human tumors decreased tumor growth and induced the tumor cells to undergo autophagy. As analysis of tumors from two patients with recurrent glioblastoma multiforme (a highly aggressive brain tumor) receiving intracranial THC administration showed signs of autophagy, the authors suggest that cannabinoid administration may provide a new approach to targeting human cancers.

Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma cells

[Duer 157099]

1. But what about in normal cells?

ER stress is not a good thing - I wonder if the effect is the same in non-cancer cells?

:shrug:

[Kip Humphrey]

7. Normal cells are too stoned to care.

[shadowknows69]

12. Duzy nomination!!!

[JeanGrey]

2. It is probably the secret to an entire cure. And we are putting

people in jail for having it.

[SammyWinstonJack]

8. Prison Industrial Complex

[pleah]

3. K&R

[NorthernSpy]

4. ***Obligatory Bob Marley Died Of Cancer Comment***

There -- no need to say it. It's already been said.


:banghead:

[Lyric]

6. Marley's death is irrelevant.

The truth is that we perceive cancer in the wrong way. Each individual cancer is incredibly different; saying that someone died of "cancer" is like saying that someone died of "virus" or "bacteria" or even "germs." Well which type?! we would ask. And so it should be for cancers.

Although viruses and bacteria are completely different from cancers, there are some parallels to be drawn. For example: we all know that there are treatments for certain viruses and bacterial infections that are as close to "cures" as we can get. However, what works like magic for one type can be totally ineffective for another. We are certain that it's the same for cancers--if and when we ever find a "cure" for a cancer, odds are that it's not going to be a universal Cure For Cancer. It'll work for one, maybe a handful of types, but probably not more than that. "Curing" cancer will involve a large spectrum of technologies and treatments that will be catered to each individual's body and their particular type of cancer.

So the lack of universal action of cannabinoids against "Cancer" (like what Marley had) is not evidence that cannabinoids are useless or ineffective. It might just have been that Bob Marley's body didn't jive with that particular treatment, or that his cancer was not one that cannabinoids are effective against--at least not alone.

I am very interested in seeing how this research goes. I am also interested in research involving bacteriophages for treatment of cancers. A friend of mine has a relative with pancreatic cancer who's undergoing a bacteriophage-delivery study. She said that he's in the control group, but if the treatment shows any real promise at this point in time, they'll administer the treatment to the control too. It's ethically required, after all.

[SOS]

16. Note

Marley died of metastatic skin melanoma.

The melanoma was discovered on his foot in Paris in 1977, but he refused to have his foot amputated.
The cancer spread to his lungs and brain much later.

He survived with metastatic melanoma for four years, which is actually remarkable.

[librechik]

19. Maybe Marley's body worked up an immunity to cannabinoids

through overexposure...

Hope not--I'm a believer in this Rx! Big Time!

[nichomachus]

21. Well, ODing on any drug isn't recommended

I had a friend who almost died from taking too much aspirin.

[panader0]

5. Autophagy- glioma- ceramide- eukaryotic -tribbles homolog

rapamycin- After all those big words I've lost my buzz.

[nichomachus]

11. Dude, they just made me laugh

[jberryhill]

14. Autophagy means the cancer cells get the munchies and eat themselves /nt

[winyanstaz]

9. There is a tea called Essiac's Tea...(appears to stop cancers)

It is also sometimes called Native Legend Tea.
Maybe science should look at this tea along with marijuana as a form of treatment. If it saves lives..we should be able to use it.
I think that is what I shall do if I ever get any cancer.

[Djinn]

10. not in a single controlled trial it hasn't

[nichomachus]

13. Yeah, funny how the researchers at big pharma can't find any benefit

to something they can't patent and make a zillion billion dollars on.

[HiFructosePronSyrup]

17. They would be able to patent it.

Under a novel use patent.

[nichomachus]

20. Yeah -- but the problem for them with most natural remedies

is that people can grow their own. Case in point, marijuana. All the drug companies can patent until they're blue in the fact, but if I can grow all I need in my backyard, their patents aren't worth shit.

[HiFructosePronSyrup]

22. Well, sure.

But then again, people can't cure cancer with plants they grow in their backyard.

You're talking real goofy conspiracy theory shit.

[Beam Me Up]

15. "no currently accepted medical use"

For marijuana to continue to remain in the same scheduling category as heroin, it has to meet the three criteria for that schedule. If it can be shown to the scientists at HHS that it does not meet one of these three criteria, then it must be removed from schedule 1. (High Times, et. al, have petitioned HHS several times for marijuana to be rescheduled. http://www.drugscience.org/lib/rsch_intro.html see also for example: http://aspe.hhs.gov/infoQuality/request&response/20b4.shtml )

http://en.wikipedia.org/wiki/Controlled_Substances_Act#Schedule_I_controlled_substances

Schedule I controlled substances
Main article: List of Schedule I drugs

"Placement on schedules; findings required
Except ... The findings required for each of the schedules are as follows:
(1) Schedule I.—
(A) The drug or other substance has a high potential for abuse.
(B) The drug or other substance has no currently accepted medical use in treatment in the United States.
(C) There is a lack of accepted safety for use of the drug or other substance under medical supervision." <9>
No prescriptions may be written for Schedule I substances, and such substances are subject to production quotas by the DEA.
Under the DEA's interpretation of the CSA, a drug does not necessarily have to have the same abuse potential as heroin or cocaine to merit placement in Schedule I (in fact, cocaine is currently a Schedule II drug due to limited medical use):<8>

[Uncle Joe]

18. Kicked for the word "autophagy" recommended for killing cancer cells.

:thumbsup:

Thanks for the thread. G_j

[opihimoimoi]

23. I can believe this shit...Its good Shit....autophagy is it now..? well, I have many of them cause I

is relative healthy with no known cancer

but I got diabetes(29 yrs) and am Pissed the stem cell research was stymied for 8 fucking years....

Re Cannibus: Take a couple hundred dollars as test the theory.....awright, maybe 10K and get this notion confirmed......

Them Pharma Boys gonna stifle this shit asap.....they make enormous Profits from any sickness....

Prevention is better than cure....