Cannabinoids induce cancer cell proliferation

[Blowmonkey]

Cannabinoids induce cancer cell proliferation via tumor necrosis factor alpha-converting enzyme (TACE/ADAM17)-mediated transactivation of the epidermal growth factor receptor.

Hart S, Fischer OM, Ullrich A.

Department of Molecular Biology, Max-Planck-Institute of Biochemistry, Am Klopferspitz 18A, D-82152 Martinsried, Germany.

Cannabinoids, the active components of marijuana and their endogenous counterparts were reported as useful analgetic agents to accompany primary cancer treatment by preventing nausea, vomiting, and pain and by stimulating appetite. Moreover, they have been shown to inhibit cell growth and to induce apoptosis in tumor cells. Here, we demonstrate that anandamide, Delta(9)-tetrahydrocannabinol (THC), HU-210, and Win55,212-2 promote mitogenic kinase signaling in cancer cells. Treatment of the glioblastoma cell line U373-MG and the lung carcinoma cell line NCI-H292 with nanomolar concentrations of THC led to accelerated cell proliferation that was completely dependent on metalloprotease and epidermal growth factor receptor (EGFR) activity. EGFR signal transactivation was identified as the mechanistic link between cannabinoid receptors and the activation of the mitogen-activated protein kinases extracellular signal-regulated kinase 1/2 as well as prosurvival protein kinase B (Akt/PKB) signaling. Depending on the cellular context, signal cross-communication was mediated by shedding of proAmphiregulin (proAR) and/or proHeparin-binding epidermal growth factor-like growth factor (proHB-EGF) by tumor necrosis factor alpha converting enzyme (TACE/ADAM17). Taken together, our data show that concentrations of THC comparable with those detected in the serum of patients after THC administration accelerate proliferation of cancer cells instead of apoptosis and thereby contribute to cancer progression in patients.

PubMed

Uhm, this is cointradictory to everything that I've read uptill now.. Someone please elaborate on the subject.

 

[BilZ0r]

Yes, I remeber when this article came out, it caused quite a stir in some of the very pro-cannabis news groups I frequent (talk.politics.drugs).

This is quite a tight article. Its published by reputable scientists, from a very reputable reaseach lab, in a reputable journal. Its introduction doesn't give away any blatant anti-cannabis biases.

The article has far too many blots for me to ever be bothered completely understanding it, and although I feel that some of the logic in it is a bit dodgy (THC has this effect, we block enzyme X and the effect stops, hence THC was activating enzyme X), the results seem sound, and show in line with other results that high doses of cannabinoids (4-10µM THC) induce cancer apoptosis.

The problem is, this thing is very in vivo. I was talking to a cancer researcher who thinks that there is nothing wrong with dealing with cancer cell lines and extrapolating; and I think that idea is rather prevalent in cancer research (the idea is laughed at in neuro circules.. 'oh, but that was in culture')

The need to implant those cell lines in an animal, and dose it with very low doses of THC.

 

[Blowmonkey]

*Bump*

Send off a copy to "Advanced Drug Discussion"..

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