Tag Archives: apoptosis

CANNABIDIOL INHIBITS ANGIOGENESIS BY MULTIPLE MECHANISMS

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“Background and purpose: Several studies demonstrated anti-proliferative and pro-apoptotic actions of cannabinoids on several tumours, together with their anti-angiogenic properties. The non-psychoactive cannabinoid cannabidiol (CBD) effectively inhibits in vitro and in vivo the growth of different types of tumours and down-regulates some pro-angiogenic signal produced by glioma cells. As its anti-angiogenic properties have not been thoroughly investigated to date, and given its very favorable pharmacological and toxicological profile, here we evaluated CBD ability to modulate tumour angiogenesis. Experimental approach: We firstly evaluated CBD effect on human umbilical vein endothelial cell (HUVEC) proliferation and viability- through MTT assay and FACS analysis-and in vitro motility-both in a classical Boyden chamber test and in a wound-healing assay. We next investigated CBD effects on different angiogenesis-related proteins released by HUVECs, using an angiogenic Array Kit and an enzyme-linked immunosorbent assay (ELISA) directed at MMP2. Afterwards we evaluated in vitro angiogenesis in treated HUVECs invading a Matrigel layer and in HUVEC spheroids embedded into collagen gels. We further characterized CBD effects using a Matrigel sponge model of in vivo angiogenesis. Key results: CBD induced HUVEC cytostasis without inducing apoptosis, inhibited HUVEC migration, invasion, and sprouting in vitro, and angiogenesis in vivo in matrigel sponges. These effects were associated with down-modulation of several angiogenesis-related molecules. Conclusions and Implications: This study reveals that CBD inhibits angiogenesis by multiple mechanisms. Its dual effect on both tumour and endothelial cells reinforces the hypothesis that CBD could represent a potential effective agent in cancer therapy.”

.http://www.ncbi.nlm.nih.gov/pubmed/22624859

Cannabidiol Induces Programmed Cell Death in Breast Cancer Cells by Coordinating the Cross-talk between Apoptosis and Autophagy

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“Cannabidiol (CBD), a major nonpsychoactive constituent of cannabis, is considered an antineoplastic agent on the basis of its in vitro and in vivo activity against tumor cells. However, the exact molecular mechanism through which CBD mediates this activity is yet to be elucidated. Here, we have shown CBD-induced cell death of breast cancer cells, independent of cannabinoid and vallinoid receptor activation. Electron microscopy revealed morphologies consistent with the coexistence of autophagy and apoptosis. Western blot analysis confirmed these findings. We showed that CBD induces endoplasmic reticulum stress and, subsequently, inhibits AKT and mTOR signaling as shown by decreased levels of phosphorylated mTOR and 4EBP1, and cyclin D1. Analyzing further the cross-talk between the autophagic and apoptotic signaling pathways, we found that beclin1 plays a central role in the induction of CBD-mediated apoptosis in MDA-MB-231 breast cancer cells. Although CBD enhances the interaction between beclin1 and Vps34, it inhibits the association between beclin1 and Bcl-2. In addition, we showed that CBD reduces mitochondrial membrane potential, triggers the translocation of BID to the mitochondria, the release of cytochrome c to the cytosol, and, ultimately, the activation of the intrinsic apoptotic pathway in breast cancer cells. CBD increased the generation of reactive oxygen species (ROS), and ROS inhibition blocked the induction of apoptosis and autophagy. Our study revealed an intricate interplay between apoptosis and autophagy in CBD-treated breast cancer cells and highlighted the value of continued investigation into the potential use of CBD as an antineoplastic agent.”

http://mct.aacrjournals.org/content/10/7/1161.long

Cannabinoid receptor 1 is a potential drug target for treatment of translocation-positive rhabdomyosarcoma

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“Because cannabinoid receptor agonists are capable of reducing proliferation and inducing apoptosis (cell death) in diverse cancer cells such as glioma, breast cancer, and melanoma, we evaluated whether CB1 is a potential drug target in rhabdomyosarcoma.

Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma in children…

 Our study shows that treatment with the cannabinoid receptor agonists HU210 (cloned THC from Hebrew University) and Delta(9)-tetrahydrocannabinol (THC from cannabis) lowers the viability of translocation-positive rhabdomyosarcoma cells through the induction of apoptosis…

These results support the notion that cannabinoid receptor agonists could represent a novel targeted approach for treatment of translocation-positive rhabdomyosarcoma.”

Full text: http://mct.aacrjournals.org/content/8/7/1838.long

A comparative study on cannabidiol-induced apoptosis in murine thymocytes and EL-4 thymoma cells

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“It has been shown that leukemia and glioma cells are sensitive to cannabidiol (CBD)-induced apoptosis (programmed cell death)….the cellular events and sensitivity to CBD-induced apoptosis between murine thymocytes and EL-4 thymoma cells were compared. Cannabidiol markedly induced apoptosis in a time- and concentration-related manner in both cells… The results demonstrated that both thymocytes and EL-4 thymoma cells were susceptible to CBD-induced apoptosis…”

http://www.ncbi.nlm.nih.gov/pubmed/18387516

Cannabidiol-induced apoptosis in primary lymphocytes is associated with oxidative stress-dependent activation of caspase-8

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“Cannabidiol-induced apoptosis in primary lymphocytes is associated with oxidative stress-dependent activation of caspase-8” and “The non-psychoactive cannabidiol triggers caspase activation and oxidative stress in human glioma cells… we have shown that the non-psychoactive cannabinoid compound cannabidiol (CBD) induces apoptosis (cell death) of glioma cells in vitro and tumor regression…”

http://www.ncbi.nlm.nih.gov/pubmed/17950393

Cannabidiol protects oligodendrocyte progenitor cells from inflammation-induced apoptosis by attenuating endoplasmic reticulum stress

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“Cannabidiol (CBD) is the most abundant cannabinoid in Cannabis sativa that has no psychoactive properties. CBD has been approved to treat inflammation, pain and spasticity associated with multiple sclerosis (MS), of which demyelination and oligodendrocyte loss are hallmarks. Thus, we investigated the protective effects of CBD against the damage to oligodendrocyte progenitor cells (OPCs) mediated by the immune system… Cannabidiol protects oligodendrocyte progenitor cells… These findings suggest that attenuation of the ER stress pathway is involved in the ‘oligoprotective’ effects of CBD during inflammation.”

http://www.ncbi.nlm.nih.gov/pubmed/22739983

Rimonabant inhibits human colon cancer cell growth and reduces the formation of precancerous lesions in the mouse colon

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“Rimonabant inhibits human colon cancer cell growth and reduces the formation of precancerous lesions…” and “Cannabinoid receptor activation induces apoptosis… in colon cancer cells”

http://www.ncbi.nlm.nih.gov/pubmed/19479993

Delta9-tetrahydrocannabinol inhibits cell cycle progression in human breast cancer cells through Cdc2 regulation.

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” Here, we show that Delta(9)-tetrahydrocannabinol (THC), through activation of CB(2) cannabinoid receptors, reduces human breast cancer cell proliferation by blocking the progression of the cell cycle and by inducing apoptosis… these data might set the bases for a cannabinoid therapy for the management of breast cancer.”

http://www.ncbi.nlm.nih.gov/pubmed/16818634

 

Cannabis-induced cytotoxicity in leukemic cell lines: the role of the cannabinoid receptors and the MAPK pathway

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“We therefore investigated the role of the CB-Rs (CannaBinoid-Receptors) in mediating apoptosis in 3 leukemic cell lines… We have shown that THC is a potent inducer of apoptosis… THC-induced cell death…”

http://bloodjournal.hematologylibrary.org/content/105/3/1214.long

Harvard Study: Marijuana Cuts Lung Cancer Tumor Growth In Half

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“The active ingredient in marijuana cuts tumor growth in common lung cancer in half and significantly reduces the ability of the cancer to spread, say researchers at Harvard University who tested the chemical in both lab and mouse studies.”

http://www.sciencedaily.com/releases/2007/04/070417193338.htm