• N&PD Moderators: Skorpio | thegreenhand

Cannabis induced cytotoxicity in leukaemic cell lines..

Blowmonkey

Bluelight Crew
Joined
Aug 15, 2003
Messages
12,450
Cannabis induced cytotoxicity in leukaemic cell lines: the role of the cannabinoid receptors and the MAPK pathway

9-tetrahydrocannabinol (THC) is the active metabolite of cannabis. THC causes cell death in vitro through the activation of complex signal transduction pathways. However, the role that the cannabinoid 1 and 2 receptors (CB1-R and CB2-R) play in this process is less clear. We therefore investigated the role of the CB-Rs in mediating apoptosis in 3 leukaemic cell lines, and performed microarray and immunoblot analyses to establish further the mechanism of cell death. We developed a novel flow cytometric technique of measuring the expression of functional receptors, and utilised combinations of selective CB1-R and CB2-R antagonists and agonists to determine their individual roles in this process. We have shown that THC is a potent inducer of apoptosis, even at 1X IC50 concentrations, and as early as six hours after exposure to the drug. These effects were seen in leukaemic cell lines (CEM, HEL-92 and HL60) as well as in peripheral blood mononuclear cells. Additionally, THC did not appear to act synergistically with cytotoxic agents such as cisplatin. One of the most intriguing findings was that THC-induced cell death was preceded by significant changes in the expression of genes involved in the MAPK signal transduction pathways. Both apoptosis and gene expression changes were altered independent of p53 and the CB-Rs.

Thomas Powles, Robert te Poele, Jonathan Shamash, Tracy Chaplin, David Propper, Simon Joel, Tim Oliver, and Wai M Liu*

New Drug Study Group, St Bartholomew's Hospital (SBH), London, United Kingdom; Dept Medical Oncology, St Bartholomew's Hospital (SBH), London, United Kingdom
Centre for Cancer Therapeutics, Institute of Cancer Research, Surrey, United Kingdom
Dept Medical Oncology, St Bartholomew's Hospital (SBH), London, United Kingdom
Dept Medical Oncology, Charterhouse Square, London, United Kingdom
New Drug Study Group, St Bartholomew's Hospital (SBH), London, United Kingdom
Barry Reed Oncology Laboratory, London, United Kingdom
http://www.bloodjournal.org/cgi/content/abstract/2004-03-1182v1
 
That is really interesting...

unfortunately for some reason I can't find the full text...

did they say the interaction was mainly CB1 or CB2 mediated? or did they not know?
probably CB2, in which case I wouldnt be entirely surprised if MAPK was involved.
but if it were CB1, the implications for neurogenesis and neuronal degeneration might be quite far ranging
 
So what is the point of this study? I didnt read much but a bunch of fancy words, I take it the publishers of this experiment/study are implying that THC is related to blood cancer?

And so what if it is - There are endless numbers of things out there that are bad for you, how many prescription drugs are pulled off the American markets after they are found to cause things like heart valve damage, strokes, etc...

Tell us something we dont know..
 
^^actually my interpretation is that if it "is a potent inducer of apoptosis" in leukimia cells, then it would help treat cancer, but I'm very much untrained in this, and could be completely wrong.
 
^ You're right. Apoptis means cell destruction to say it simple. THC induces cell destruction in leukemia. I hope it's somewhat clearer now.

Meanwhile, can I remind you of the fact that this is "Advanced Drug Discussion" and there may be lots of things that only look like fancy words to you, but actually have meaning. So don't be so quick to jump to conclusions.
 
Hmm the connection gets stronger and stronger. More research is definetly needed. Apart from that, new medicines are always good. But at the moment some forms of leukemia can be healed quite ok.
 
I stand corrected.. I've veeb smoking too much pot myself lately, lol..

My bad though, I apologize, and will remain more open minded in the future, cheers!
 
actually, there is a technical difference

apoptosis refers to an external signal, eg tumour necrosis factor alpha binding to its receptor induces cell death.

programmed cell death is internal. for example, there is a DNA mutation and P53 induces bax, bad etc. which activates the apoptosome.

both cascades lead to caspase 3 activation, which is the 'executioner caspase' and kills the cell by usual 'apoptotic/PCD' means

'programmed cell death' is one of my favourite terms in biology :D
 
can you elaborate on that caspase 3 activation any further?
 
Top