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8 May 2008
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THC inhibits breast cancer cell proliferation through JunD
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MedWire News: Tetrahydrocannabinol is a potent inhibitor of proliferation in cultured breast cancer cells and exerts its effect through the JunD transcription factor complex, researchers report.
There is increasing evidence that cannabinoids, the active components of marijuana, possess antitumoral properties by inhibiting proliferation and angiogenesis or promoting apoptosis.
A previous study reported by MedWire News showed that cannabidiol, a non-toxic phytocannabinoid, can inhibit breast cancer spread in a rodent model of the disease.
In the present study, Cristina Sanchez (Complutense University, Madrid, Spain) and colleagues turned their attention to the more potent plant-derived cannabinoid, Δ9-tetrahydrocannabinol (THC).
The researchers treated EVSA-T human breast cancer cells with increasing concentrations of THC up to 5 µm for 24 hours and analyzed gene expression profiles using microarray analysis.
THC inhibited the proliferation of EVSA-T cells in a dose-dependent manner.
A panel of 28 genes showed differential expression in response to THC treatment, of which 12 were downregulated and 16 were upregulated with increasing THC concentration.
Three of the upregulated genes were transcription factors, namely Id2, JunD, and Zfp36L1.
Since Id2 had previously been investigated in the study on cannabidiol, the researchers focused on JunD.
Real-time quantitative polymerase chain reaction analysis confirmed that JunD expression was upregulated around 2.6-fold in THC-treated EVSA-T cells relative to non-treated cells. Interestingly, THC had no effect on non-malignant human mammary epithelial cells.
Next, the researchers used confocal microscopy to track radiolabeled JunD protein within EVSA-T cells. They found that JunD was localized to the nucleus upon THC treatment, consistent with its role as a DNA-binding transcription factor.
Finally, the researchers ablated JunD expression in EVSA-T cells using a complementary short interfering RNA signal. THC treatment had little antiproliferative effect on these cells. Notably two genes previously unregulated by THC, namely, cyclin-dependent kinase inhibitor p27 and the tumor suppressor gene testin, were static in cells where JunD was blocked.
"These findings point therefore to a new target to inhibit breast cancer progression, which may contribute to the design of efficient treatments for this malignancy,' Sanchez et al conclude in the journal Oncogene.
Oncogene 2008; Advance online publication
http://www.nature.com/onc/index.html
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© 2006 CMG
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