Monthly Archives: September 2013

Enhancing the in vitro cytotoxic activity of Delta9-tetrahydrocannabinol in leukemic cells through a combinatorial approach.

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“Delta(9)-Tetrahydrocannabinol (THC) is the active metabolite of cannabis, which has demonstrable cytotoxic activity in vitro. In support of our previously published data, we have investigated the interactions between THC and anti-leukemia therapies and studied the role of the signalling pathways in mediating these effects.

 Results showed clear synergistic interactions between THC and the cytotoxic agents in leukemic cells…

 Overall, these results demonstrate for the first time that a combination approach with THC and established cytotoxic agents may enhance cell death in vitro. Additionally the MAPK/ERK pathway appears responsible in part for these effects.”

http://www.ncbi.nlm.nih.gov/pubmed/18608861

Cannabidiol-Induced Apoptosis in Human Leukemia Cells: A Novel Role of Cannabidiol in the Regulation of p22phox and Nox4 Expression

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“Marijuana has been suggested as a potent therapeutic agent alleviating such complications as intraocular pressure in glaucoma and cachexia, nausea, and pain in AIDS and cancer patients. A number of recent studies now suggest the possible use of these compounds for the treatment of cannabinoid receptor-expressing tumors…

In the current study, we examined the effects of the nonpsychoactive cannabinoid, cannabidiol, on the induction of apoptosis in leukemia cells. Exposure of leukemia cells to cannabidiol led to cannabinoid receptor 2 (CB2)-mediated reduction in cell viability and induction in apoptosis. Furthermore, cannabidiol treatment led to a significant decrease in tumor burden and an increase in apoptotic tumors in vivo…

Together, the results from this study reveal that cannabidiol, acting through CB2 and regulation of Nox4 and p22phox expression, may be a novel and highly selective treatment for leukemia…

In summary, the current study demonstrates that CBD-induced apoptosis may constitute a novel approach to treat malignancies of the immune system…”

Full text: http://molpharm.aspetjournals.org/content/70/3/897.long

Cannabidiol, unlike synthetic cannabinoids, triggers activation of RBL-2H3 mast cells

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“Plant-derived cannabinoids, such as Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), the main psychoactive and nonpsychoactive components of cannabis, respectively, possess myriad pharmacological properties…

Cannabidiol (CBD), a prominent psychoinactive component of cannabis with negligible affinity for known cannabinoid receptors, exerts numerous pharmacological actions, including anti-inflammatory and immunosuppressive effects…

Together, these results support existence of yet-to-be identified sites of interaction, i.e., receptors and/or ion channels associated with Ca2+ influx of natural cannabinoids such as CBD and THC, the identification of which has the potential to provide for novel strategies and agents of therapeutic interest.”

Full text: http://www.jleukbio.org/content/81/6/1512.long

Gamma-irradiation enhances apoptosis induced by cannabidiol, a non-psychotropic cannabinoid, in cultured HL-60 myeloblastic leukemia cells.

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“Two non-psychotropic cannabinoids, cannabidiol (CBD) and cannabidiol-dimethylheptyl (CBD-DMH), induced apoptosis in a human acute myeloid leukemia (AML) HL-60 cell line…

  Caspase-3 activation was observed after the cannabinoid treatment, and may represent a mechanism for the apoptosis.

Our data suggest a possible new approach to treatment of AML.”

http://www.ncbi.nlm.nih.gov/pubmed/14692532

Tetrahydrocannabinol inhibits adenyl cyclase in human leukemia cells.

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“Delta 9-tetrahydrocannabinol has been shown to induce incomplete maturation in ML2 human leukemia cell lines.

We extend the observation of its induction of morphologic maturation to HL60 cells and of its induction of growth restriction to HL60 and K562 cells.

 We show that tetrahydrocannabinol reduces the cyclic AMP content of ML2 cells.

 Finally we demonstrate that this agent inhibits adenyl cyclase activity in ML2 cell membrane-enriched fractions.

This finding in myeloid cells is compatible with one hypothesis of cannabinoid action in neuronal cells.”

http://www.ncbi.nlm.nih.gov/pubmed/2154651

Cannabinoids induce incomplete maturation of cultured human leukemia cells.

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“Monocyte maturation markers were induced in cultured human myeloblastic ML-2 leukemia cells after treatment for 1-6 days with 0.03-30 microM delta 9-tetrahydrocannabinol (THC), the major psychoactive component of marijuana…

 Cannabinoids induce incomplete maturation of cultured human leukemia cells…

Findings obtained from this system may have important implications for studies of cannabinoid effects on normal human bone-marrow progenitor cells.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC298868/

Targeting CB2 cannabinoid receptors as a novel therapy to treat malignant lymphoblastic disease

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“In the current study, we examined whether ligation of CB2 receptors would lead to induction of apoptosis in tumors of immune origin and whether CB2 agonist could be used to treat such cancers.

 Exposure of murine tumors EL-4, LSA, and P815 to delta-9-tetrahydrocannabinol (THC) in vitro led to a significant reduction in cell viability and an increase in apoptosis…

Culture of primary acute lymphoblastic leukemia cells with THC in vitro reduced cell viability and induced apoptosis.

Together, the current data demonstrate that CB2 cannabinoid receptors expressed on malignancies of the immune system may serve as potential targets for the induction of apoptosis. Also, because CB2 agonists lack psychotropic effects, they may serve as novel anticancer agents to selectively target and kill tumors of immune origin.”

http://bloodjournal.hematologylibrary.org/content/100/2/627.long

“We examined whether treatment of tumor-bearing mice with THC was effective at killing tumor cells in vivo… These data suggest that THC was effective in vivo to induce apoptosis and kill the tumor cells… THC treatment can cure tumor-bearing mice… they were completely cured…Taken together, these results suggest that THC can exert anticancer properties in vivo.” http://bloodjournal.hematologylibrary.org/content/100/2/627.long?sso-checked=1

 

Targeting cannabinoid receptors to treat leukemia: role of cross-talk between extrinsic and intrinsic pathways in Delta9-tetrahydrocannabinol (THC)-induced apoptosis of Jurkat cells.

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“Targeting cannabinoid receptors has recently been shown to trigger apoptosis and offers a novel treatment modality against malignancies of the immune system.

  In this study, we used human Jurkat leukemia cell lines with defects in intrinsic and extrinsic signaling pathways to elucidate the mechanism of apoptosis induced by Delta9-tetrahydrocannabinol (THC)…

Together, these data suggest that the intrinsic pathway plays a more critical role in THC-induced apoptosis while the extrinsic pathway may facilitate apoptosis via cross-talk with the intrinsic pathway.”

http://www.ncbi.nlm.nih.gov/pubmed/15978942

Cannabinoid-receptor expression in human leukocytes.

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“Marijuana and many of its constituent cannabinoids influence the central nervous system (CNS), probably through the cannabinoid receptor, which has recently been cloned in rat and human. While numerous reports have also described effects of cannabinoids on the immune system, the observation of both mRNA and cannabinoid receptor has hitherto been exclusively confined to the brain, a reported detection in the testis being the sole example of its presence at the periphery.

Here we report the expression of the cannabinoid receptor on human immune tissues using a highly sensitive polymerase-chain-reaction-based method for mRNA quantification. We show that, although present in a much lower abundance than in brain, cannabinoid receptor transcripts are found in human spleen, tonsils and peripheral blood leukocytes…

The demonstration of cannabinoid-receptor expression at both mRNA and protein levels on human leukocytes provides a molecular basis for cannabinoid action on these cells.”

http://www.ncbi.nlm.nih.gov/pubmed/8508790

Anticancer activity of anandamide in human cutaneous melanoma cells.

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“Cannabinoids are implicated in the control of cell proliferation, but little is known about the role of the endocannabinoid system in human malignant melanoma. This study was aimed at characterizing the in vitro antitumor activity of anandamide (AEA) in A375 melanoma cells…

 Overall, these findings demonstrate that AEA induces cytotoxicity against human melanoma cells in the micromolar range of concentrations through a complex mechanism, which involve COX-2 and LOX-derived product synthesis and CB1 activation. Lipid raft modulation, probably linked to GPR55 activation, might also have a role.”

http://www.ncbi.nlm.nih.gov/pubmed/24041928