Br J Clin Pharmacol. Feb;75(2) doi: /j x. Cannabidiol as potential anticancer drug. Massi P(1), Solinas M, Cinquina. Over the past years, several lines of evidence support an antitumourigenic effect of cannabinoids including Δ9-tetrahydrocannabinol (Δ9-THC). Request PDF on ResearchGate | Cannabidiol as potential anticancer drug | Over the past years, several lines of evidence support an.
anticancer drug Cannabidiol as potential
It has also been proposed that cbd might activate trpv 2 receptors to promote glioma cell death In cancer cells, cannabinoids block the activation of the vascular endothelial growth factor vegf pathway, an inducer of angiogenesis. Specifically, various elements of the cascade, such as the main ligand vegf and the active forms of its main receptors vegfr 1 and vegfr 2 , are downregulated with cannabinoid treatment of skin carcinomas 54 , gliomas 32 , 61 , and thyroid carcinomas In vascular endothelial cells, cannabinoid receptor activation inhibits proliferation and migration, and induces apoptosis 61 , Those and perhaps other cannabinoid-evoked actions result in a normalized tumour vasculature—that is, smaller and fewer vessels that are more differentiated and less leaky.
Likewise, cb 1 or cb 2 receptor agonists or both reduce the formation of distant tumour masses in animal models of both induced and spontaneous metastasis, and inhibit adhesion, migration, and invasiveness of glioma 64 , breast 65 , 66 , lung 67 , 68 , and cervical 68 cancer cells in culture.
Those effects depend, at least in part, on the modulation of extracellular proteases such as matrix metalloproteinase 2 64 and their inhibitors such as tissue inhibitor of matrix metalloproteinases 1 Notably, pharmacologic inhibition of ceramide biosynthesis abrogates the antitumour and antiangiogenic effect of cb 1 or cb 2 receptor agonists or both in glioma xenografts, and decreases vegf production by glioma cells in vitro and in vivo Likewise, inhibition of matrix metalloproteinase 2 expression and glioma cell invasion is prevented by blocking ceramide biosynthesis and by knocking down p8 expression It is worth noting that cbd , by acting independently of the cb 1 and cb 2 receptors, produces a remarkable anti-tumour effect—including reduction of invasiveness and metastasis—in various animal models of cancer.
This effect of cbd seems to rely, at least in part, on the downregulation of the helix-loop-helix transcription factor inhibitor of dna binding 1 69 , Notably, stimulation of cannabinoid receptors can lead to important changes in the processes that regulate anti-tumour immunity. Thus, for example, treatment of mice with thc triggers a shift from Th1 to Th2 of cytokine profile 20 , 71 — 73 and induces mobilization of myeloid-derived suppressor cells 74 , two events that play a critical role in the suppression of antitumour immunity.
In agreement with that notion, stimulation of cb 2 has been proposed in some reports to enhance tumourigenesis by interfering with tumour surveillance by the immune system 20 , By contrast, cannabinoids can also enhance immune system—mediated tumour surveillance in some contexts: Those observations might be related to the ability of thc to reduce inflammation 75 , 76 , an effect that might prevent certain types of cancer 76 , For cannabinoid use to be clinically successful, anti-tumour effects will have to overcome immunosuppressive potentially tumour-promoting effects.
Additional studies should clarify the issue. For example, it could be conceivable to study the effect of cannabinoid administration on the generation and progression of tumours with varying sensitivity to cannabinoids and generated in immunocompetent or immunodeficient mice in which the expression of cb 1 or cb 2 receptors or both in cells from the immune system has been genetically manipulated. Numerous studies have contributed to an appreciation of the heterogeneity of cancer, whereby each subtype of cancer—and even each individual tumour—exhibits a series of molecular characteristics that determines its behaviour and, in particular, its responsiveness to various anticancer drugs.
In agreement with that line of reasoning, a recent report investigated the molecular features associated with the resistance of a collection of human glioma cell lines and primary cultures to cannabinoid antitumour action The study showed that, although the apoptotic effect of thc on glioma cells relied on the stimulation of cannabinoid receptors and activation of the p8-mediated autophagy pathway, the differences in the sensitivity to thc -induced cell death correlated with enhanced expression of a particular set of genes in the thc -resistant glioma cells rather than with the presence of different expression levels of cb 1 or cb 2 receptors Interestingly, upregulation of one of those genes, midkine MDK , which encodes a growth factor that was previously associated with increased malignancy and resistance to anticancer therapies in several types of tumours 77 , 78 , correlates with lower overall survival in patients with glioblastoma Moreover, mdk plays a direct role in the resistance to thc action through stimulation of anaplastic lymphoma kinase alk Thus, the stimulation of alk by mdk inhibits the thc -evoked autophagy-mediated cell-death pathway.
Further research should clarify whether that mechanism could also be responsible for the resistance to other therapies of cancer cells expressing high levels of mdk. Interestingly, in vivo silencing of MDK or pharmacologic inhibition of alk in a mouse xenograft model abolishes the resistance to thc treatment of established tumours derived from cannabinoid-resistant glioma cells Taken together, the foregoing findings support the idea that stimulation of the mdk — alk axis promotes resistance to thc antitumour action in gliomas and could help to set a foundation for the potential clinical use of thc in combination with inhibitors of the mdk — alk axis Figure 2.
Glioblastoma is highly resistant to current anticancer therapies 80 — Specifically, resistance of glioma cells to cannabinoid-induced cell death relies, at least in part, on enhanced expression of mdk and the subsequent activation of alk Likewise, enhanced expression of the heparin-bound epidermal growth factor receptor egfr ligand amphiregulin can promote resistance to thc antitumour action by stimulation of extracellular signal-regulated kinase erk The combination of thc with pharmacologic inhibitors of alk or genetic inhibition of MDK enhances cannabinoid action in resistant tumours, which provides a rationale for the design of targeted therapies capable of increasing cannabinoid antineoplastic activity Combinations of cannabinoids with classical chemotherapeutic drugs such as the alkylating agent temozolomide the benchmark agent for the management of glioblastoma 80 , 84 have been shown to produce a strong anticancer action in animal models Combining cannabinoids and temozolomide is thus a very attractive possibility for clinical studies aimed at investigating cannabinoid antitumour effects in glioblastoma.
Other potentially interesting strategies to enhance cannabinoid anticancer action still requiring additional experimental support from data obtained using preclinical models could be to combine cannabinoids with er stress or autophagy inducers or both or with inhibitors of the m torc 1 axis. In line with that idea, alk inhibitors have started to be used in clinical trials for the management of non-small-cell lung cancer and other types of tumours 86 , Future research should clarify whether this mechanism of resistance to cannabinoid action operates in other types of tumours.
In agreement with that possibility, MDK silencing enhanced the sensitivity of cannabinoid-resistant pancreatic cancer cells to thc -induced cell death The release by cancer cells of other growth factors has also been implicated in the mechanism of resistance to cannabinoid antitumour action. Thus, increased expression of amphiregulin is associated with enhanced resistance to thc antitumour action in glioma xenografts Notably illustrating how the dose of cannabinoids could be crucial for optimal therapeutic effect, low submicromolar concentrations of thc or other synthetic cannabinoid agonists enhance the proliferation of several cancer cell lines in vitro.
That effect relies on activation of the protease adam 17, the shedding of heparin-bound egfr ligands including amphiregulin and the subsequent stimulation of the erk and akt pathways In line with that idea, a recent report showed that treatment with the synthetic cannabinoid CP 55, increases the proliferation of murine glioma cells engineered to express cb 1 or cb 2 receptors only when those receptors are coupled to akt activation Although a pro-tumourigenic effect has not been observed for the growth of tumour xenografts generated with glioma cells and treated with low doses of thc 85 , increased expression of amphiregulin promotes resistance to thc antitumour action through a mechanism that involves the egfr -dependent stimulation of erk and the subsequent inhibition of p8 and trb 3 expression.
Likewise, pharmacologic inhibition of egfr , erk 83 , or akt enhances the cell-death-promoting action of thc in glioma cultures unpublished observations by the authors , which suggests that targeting egfr and the akt and erk pathways could enhance the antitumour effect of cannabinoids. The use of combinational anticancer therapies has a number of theoretical advantages over single-agent strategies, because they allow for the simultaneous targeting of tumour growth, progression, and spread at various levels.
In line with that idea, recent observations suggest that the combined administration of cannabinoids with other anticancer drugs acts synergistically to reduce tumour growth. For example, the administration of thc and temozolomide exerts strong antitumour action in glioma xenografts, an effect that is also evident in temozolomide-resistant tumours A similar effect was observed when thc and cbd were combined with radiotherapy in animal models of glioma.
Interestingly, no toxicity was observed in mice treated with combinations of thc and temozolomide Because most patients with glioblastoma undergo temozolomide treatment, the foregoing findings indicate that the combined administration of temozolomide and cannabinoids could be therapeutically exploited for the management of glioblastoma Figure 2 and perhaps other tumour types such as melanoma Likewise, another study recently showed that the combined administration of gemcitabine the benchmark agent for the treatment of pancreatic cancer and various cannabinoid agonists synergistically reduced the viability of pancreatic cancer cells Other reports indicated that anandamide and HU might also enhance the anticancer activity of paclitaxel 89 and 5-fluorouracil 90 respectively.
An additional approach has been to combine thc with cbd , a phytocannabinoid that reduces although to a lower extent than thc the growth of several types of tumour xenografts through a still poorly-defined mechanism 59 , 91 , Combined administration of thc and cbd enhances the anticancer activity of thc and reduces the dose of thc needed to induce its tumour growth-inhibiting activity 85 , Moreover, the combination of thc and cbd together with temozolomide produces a striking reduction in the growth of glioma xenografts even when low doses of thc are used Likewise, the combination of thc , cbd , and radiotherapy also produced clear anticancer activity in an orthotopic model of glioma Notably, cbd was also shown to alleviate some of the undesired effects of thc administration such as convulsions, discoordination, and psychotic events, thus improving the tolerability of cannabis-based medicines As mentioned earlier, C.
Thus, we think that clinical studies aimed at analyzing the efficacy of cannabinoids as antitumour agents should be based on the use both of pure substances, such as thc and cbd , and of cannabis extracts containing controlled amounts of thc , cbd , and other cannabinoids. The clinical approval of cannabinoids is largely restricted to palliative uses in various diseases, but since the emergence of promising preclinical data, the antitumour effects of cannabinoids are beginning to be clinically assessed.
In a pilot phase i clinical study, 9 patients with actively- growing recurrent glioblastoma for whom standard therapy had previously failed underwent intracranial thc administration Under those conditions, cannabinoid delivery was safe and could be achieved without significant unwanted effects. In addition, although no statistically significant conclusions can be extracted from a cohort of 9 patients, the results obtained in the study suggest that some patients responded—at least partially—to thc treatment in terms of a decreased tumour growth rate as evaluated by magnetic resonance imaging Importantly, analyses of samples obtained from 2 study patients before and after thc administration indicated that the molecular mechanism of cannabinoid antitumour action—namely, p8 and trib 3 upregulation 35 , 37 , m torc 1 inhibition 37 , stimulation of autophagy and apoptosis 11 , 35 , 37 , inhibition of cell proliferation 11 , decreased vegf signalling 32 , and matrix metalloproteinase 2 downregulation 64 delineated here earlier —also operates in vivo.
Those findings were encouraging and reinforced interest in the potential use of cannabinoids in cancer therapies.
However, they also highlighted the need for further research aimed at optimizing the use of cannabinoids in terms of patient selection, combination with other anti-cancer agents, and use of other routes of administration. Administration of endocannabinoids or inhibitors of endocannabinoid-degrading enzymes has been shown to reduce the growth of various tumour xenograft types 95 , 96 and could therefore be a reasonable strategy for targeting cannabinoid receptors for anticancer purposes.
However, as discussed here earlier, the role of the endocannabinoid system, including the endocannabinoid-degrading enzymes, in the control of tumour generation and progression is not well understood. Because enhancing endocannabinoid tone only has mild antitumour effects in mice and because no inhibitor of endocannabinoid degradation has yet been approved for use in humans, clinical studies aimed at analyzing the efficacy of cannabinoids as antitumour agents should be based on the use of plant-derived or synthetic agonists of cannabinoid receptors rather than on endocannabinoids or inhibitors of endocannabinoid degradation.
The long-known therapeutic properties of C. As already mentioned, C. However, pure drugs are more prone to standardization than complex molecular cocktails. Thus, it would be ideal for studies aiming to investigate the anticancer actions of cannabinoids in patients to be performed comparatively with both pure substances and cannabis extracts containing controlled amounts of thc , cbd , and other cannabinoids.
The most widely used route of administration for recreational and self-medicating marijuana is smoking. Although thc and other phytocannabinoids are rapidly absorbed by inhalation, smoking is an unattractive clinical option. Preclinical work in animal models has typically used peri-tumoural administration of cannabinoids. Likewise, in the only clinical trial in which a cannabinoid was assayed as an antitumour agent, thc was administered locally intracranial delivery to patients with glioblastoma multiforme Nevertheless, this route of administration has many obvious limitations.
Currently available cannabis-based medicines are administered as capsules or using an oromucosal spray Preclinical animal models have yielded data indicating that systemic oral or intraperitoneal administration of cannabinoids effectively decreases tumour growth GV, CS, and MG. Unpublished observations , and so it seems reasonable that future clinical studies with the goal of determining the efficacy of cannabinoids as antitumour agents use oral or oromucosal routes of administration.
Two currently ongoing clinical trials could shed some light on these issues. The other is a phase ii trial aimed at evaluating the effect of cbd as single treatment in patients with solid tumours https: Hopefully, in the near future, new clinical trials will start, helping to determine whether cannabinoids can be used, for other than their palliative effects, in the treatment of cancer patients.
It is widely believed that strategies aimed at reducing mortality from cancer should consist of targeted therapies capable of providing the most efficacious and selective treatment for each individual tumour and patient. Thus, the major focus of anticancer drug development has progressively moved from nonspecific chemotherapies to molecularly-targeted inhibitors.
However, despite the huge amount of preclinical literature on how these rationally designed compounds work, their use in clinical practice is still limited. How do cannabinoid-based medicines fit into this ongoing scenario? Consider glioma, the type of cancer in which the most detailed cannabinoid research has been conducted to date. As discussed here, engagement of a molecular target the cb receptors by a family of selective drugs thc and other cannabinoid agonists inhibits tumour growth in animal models through a well-established mechanism of action that also seems to operate in human patients.
Moreover, cannabinoids potentiate the antitumour efficacy of temozolomide and alk inhibitors in mice harbouring gliomas.
However, further research is required to define the precise molecular cross-talk between cannabinoids and chemotherapeutic drugs and to optimize the pharmacology of preclinical cannabinoid-based combination therapies. With respect to patient stratification, the particular individuals that are potentially responsive to cannabinoid administration should be unequivocally determined.
To that end, high-throughput approaches should be implemented to find cannabinoid therapy—associated biomarkers in tumour biopsies or, ideally, in easily acquired fluids containing circulating cancer cells or enhanced levels of resistance factors that might have been released by cancer cells. Such biomarkers would conceivably relate to cannabinoid pharmacodynamics—namely, expression and activity of cannabinoid receptors and their downstream cell-death-inducing effectors.
The approach would be analogous to the biochemical evaluation of estrogen and ErbB2 receptors, which respectively predict benefit from endocrine therapies and trastuzumab in breast cancer. Predictive markers to define the sensitivity of a particular tumour to cannabinoid-based therapies could also include the status of growth factors, such as mdk in gliomas, and their receptors and signalling partners. To summarize, cannabinoids induce tumour cell death and inhibit tumour angiogenesis and invasion in animal models of cancer, and there are indications that they act similarly in patients with glioblastoma.
Given that cannabinoids show an acceptable safety profile, clinical trials testing them as single drugs or, ideally, in combination therapies in glioblastoma and other types of cancer are both warranted and urgently needed. GW Pharmaceuticals and Cellmid fund part of the research conducted by our laboratory. Likewise, a portion of the data obtained by the authors concerning the antitumoural action of cannabinoids is included in three patent applications presented by GW Pharmaceuticals.
Gaoni Y, Mechoulam R. Isolation, structure and partial synthesis of an active constituent of hashish. J Am Chem Soc ; The diverse cb 1 and cb 2 receptor pharmacology of three plant cannabinoids: Br J Pharmacol ; Isolation and structure of a brain constituent that binds to the cannabinoid receptor.
Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochem Biophys Res Commun ; International Union of Basic and Clinical Pharmacology. Cannabinoid receptors and their ligands: Structure of a cannabinoid receptor and functional expression of the cloned c dna. Molecular characterization of a peripheral receptor for cannabinoids. Cannabinoid cb 2 receptor: Trends Pharmacol Sci ; Atwood BK, Mackie K.
A pilot clinical study of delta9-tetrahydrocannabinol in patients with recurrent glioblastoma multiforme. Br J Cancer ; Cannabinoids for cancer treatment: Katona I, Freund TF. Endocannabinoid signaling as a synaptic circuit breaker in neurological disease. The endocannabinoid system as an emerging target of pharmacotherapy. Emerging strategies for exploiting cannabinoid receptor agonists as medicines.
Nat Rev Cancer ;3: Towards the use of cannabinoids as antitumour agents. Nat Rev Cancer ; The expression level of cb 1 and cb 2 receptors determines their efficacy at inducing apoptosis in astrocytomas.
Deltatetrahydrocannabinol enhances breast cancer growth and metastasis by suppression of the antitumor immune response. Deltatetrahydrocannabinol inhibits antitumour immunity by a cb 2 receptor-mediated, cytokine-dependent pathway. Update on the endocannabinoid system as an anticancer target.
Expert Opin Ther Targets ; Inhibition of glioma growth in vivo by selective activation of the cb 2 cannabinoid receptor. Delta9-tetrahydrocannabinol inhibits cell cycle progression in human breast cancer cells through Cdc2 regulation. Monoacylglycerol lipase regulates a fatty acid network that promotes cancer pathogenesis. Fatty acid amide hydrolase in prostate cancer: The cannabinoid receptors are required for ultraviolet-induced inflammation and skin cancer development.
Role of cannabinoid receptor cb 2 in her 2 pro-oncogenic signaling in breast cancer. J Natl Cancer Inst ; Loss of cannabinoid receptor 1 accelerates intestinal tumor growth. Increased endocannabinoid levels reduce the development of precancerous lesions in the mouse colon. J Mol Med Berl ; Cannabinoids inhibit the vascular endothelial growth factor pathway in gliomas.
Antitumoral action of cannabinoids: De novo—synthesized ceramide is involved in cannabinoid-induced apoptosis. The stress-regulated protein p8 mediates cannabinoid-induced apoptosis of tumor cells.
J Biol Chem ; Cannabinoid action induces autophagy-mediated cell death through stimulation of er stress in human glioma cells. J Clin Invest ; Linking er stress to autophagy: Int J Cell Biol ; Autophagy fights disease through cellular self-digestion. Life and death partners: Cell Death Differ ; Autophagy in malignant transformation and cancer progression. Besides the in vitro data, the efficacy of CBD in reducing tumour growth and, in some cases, metastasization was confirmed in experimental animal models.
However, the potential clinical application of CBD for cancer therapy needs some consideration. Its low toxicity is certainly a good starting point.
The route of administration appears more problematic since CBD oral absorption is slow and unpredictable. Interestingly, this range of concentration was demonstrated to be active in inhibiting lung cancer cell invasion [ 52 , 53 ], thus suggesting that in some cases the oral route could be the appropriate choice.
Moreover, oromucosal administration may represent a first choice in the presence of nausea and vomiting. In the light of its safety record and considering that CBD is already currently used in patients with multiple sclerosis, the findings here summarized suggest that CBD might be worthy of clinical consideration for cancer therapy. National Center for Biotechnology Information , U.
Br J Clin Pharmacol. Published online Apr Author information Article notes Copyright and License information Disclaimer. Received Jan 30; Accepted Apr This article has been cited by other articles in PMC. Open in a separate window.
Cannabinoids in the treatment of cancer Cannabinoids are currently used in cancer patients to palliate wasting, emesis and pain that often accompany cancer. Table 1 Effects of cannabidiol on different types of cancer. CBD and breast cancer In Ligresti et al. CBD and glioma CBD also possesses anti-tumoural properties in gliomas, tumours of glial origin characterized by a high morphological and genetic heterogeneity and considered one of the most devastating neoplasms, showing high proliferative rate, aggressive invasiveness and insensitivity to radio- and chemotherapy.
CBD and lung cancer Given the poor response of lung cancer to available therapy and its aggressive biological nature, a series of targets and new therapeutic strategies for their treatment are currently being investigated [ 47 — 50 ]. CBD and endocrine tumours Thyroid cancer is the most common endocrine malignancy and Ligresti et al. CBD and colon cancer Colon cancer is a major cause of morbidity and mortality in Western countries. CBD and angiogenesis Angiogenesis consists of the formation of new blood vessels from pre-existing ones and represents another promising therapeutic target for cancer therapy.
Conclusion and future directions Collectively, the non-psychoactive plant-derived cannabinoid CBD exhibits pro-apoptotic and anti-proliferative actions in different types of tumours and may also exert anti-migratory, anti-invasive, anti-metastatic and perhaps anti-angiogenic properties.
Prostaglandins Other Lipid Mediat. Identification and functional characterization of brainstem cannabinoid CB2 receptors. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. A second endogenous cannabinoid that modulates long-term potentiation. Biochemistry, pharmacology and physiology of 2-arachidonoylglycerol, an endogenous cannabinoid receptor ligand. Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors.
The molecular logic of endocannabinoid signalling. An introduction to the endocannabinoid system: Di Marzo V, Petrosino S. Endocannabinoids and the regulation of their levels in health and disease. Anandamide and vanilloid TRPV1 receptors. The orphan receptor GPR55 is a novel cannabinoid receptor. International Union of Basic and Clinical Pharmacology. Cannabinoid receptors and their ligands: Coevolution between cannabinoid receptors and endocannabinoid ligands. The endocannabinoid system as an emerging target of pharmacotherapy.
Antineoplastic activity of cannabinoids. J Natl Cancer Inst. Anti-tumoral action of cannabinoids: Inhibition of glioma growth in vivo by selective activation of the CB 2 cannabinoid receptor. Inhibition of skin tumour growth and angiogenesis in vivo by activation of cannabinoid receptors.
Cannabinoid receptors as novel targets for the treatment of melanoma. Cannabinoids induce apoptosis of pancreatic tumor cells via endoplasmic reticulum stress-related genes. Cannabinoid receptor activation induces apoptosis through tumor necrosis factor alpha-mediated ceramide de nono synthesis in colon cancer cells.
Bifulco M, Di Marzo V. Targeting the endocannabinoid system in cancer therapy: Endocannabinoids in endocrine and related tumours. Antitumorigenic effects of cannabinoids beyond apoptosis.
J Pharmacol Exp Ther. Cannabidiol displays unexpectedly high potency as an antagonist of CB1 and CB2 receptor agonists in vitro. Antitumor activity of plant cannabinoids with emphasis on the effect of cannabidiol on human breast carcinoma. Cannabidiol as a novel inhibitor of Id-1 gene expression in aggressive breast cancer cells. Pathways mediating the effects of cannabidiol on the reduction of breast cancer cell proliferation, invasion, and metastasis.
Breast Cancer Res Treat. Cannabidiol induces programmed cell death in breast cancer cells by coordinating the cross-talk between apoptosis and autophagy. Caspase-mediated cleavage of Beclin-1 inactivates Beclininduced autophagy and enhances apoptosis by promoting the release of proapoptotic factors from mitochondria. Serum-dependent effects of tamoxifen and cannabinoids upon C6 glioma cell viability. Antitumor effects of cannabidiol, a nonpsychoactive cannabinoid, on human glioma cell lines.
The non-psychoactive cannabidiol triggers caspase activation and oxidative stress in human glioma cells. Cell Mol Life Sci. Cannabidiol enhances the inhibitory effects of delta9-tetrahydrocannabinol on human glioblastoma cell proliferation and survival.
A combined preclinical therapy of cannabinoids and temozolomide against glioma. Cannabidiol, a non-psychoactive cannabinoid compound, inhibits human glioma cell migration and invasiveness. Cannabidiol inhibits human glioma cell migration through a cannabinoid receptor-independent mechanism.
Gamma-irradiation enhances apoptosis induced by cannabidiol, a non-psychotropic cannabinoid, in cultured HL myeloblastic leukemia cells. Cannabidiol-induced apoptosis in human leukemia cells: Targeting CB2 cannabinoid receptors as a novel therapy to treat malignant lymphoblastic disease.
Identification of putative oncogenes in lung adenocarcinoma by a comprehensive functional genomic approach. Novel combinations based on epidermal growth factor receptor inhibition. Lysyl oxidase is essential for hypoxia-induced metastasis. Advances in chemotherapy of non-small cell lung cancer. Cannabidiol inhibits cancer cell invasion via upregulation of tissue inhibitor of matrix metalloproteinases Decrease of plasminogen activator inhibitor-1 may contribute to the anti-invasive action of cannabidiol on human lung cancer cells.
Ramer R, Hinz B. Inhibition of cancer cell invasion by cannabinoids via increased expression of tissue inhibitor of matrix metalloproteinases A comparative study on cannabidiol-induced apoptosis in murine thymocytes and EL-4 thymoma cells. Cannabidiol-induced apoptosis in primary lymphocytes is associated with oxidative stress-dependent activation of caspase Chemopreventive effect of the non-psychotropic phytocannabinoid cannabidiol on experimental colon cancer.
Cannabidiol as potential anticancer drug
Cannabidiol as potential anticancer drug. Article date: February By: Paola Massi, Marta Solinas, Valentina Cinquina, Daniela Parolaro, in Volume Over the past years, several lines of evidence support an antitumourigenic effect of cannabinoids including Δ9‐tetrahydrocannabinol (Δ9‐THC). Cannabidiol as potential anticancer drug. Subject: Cancer - PUBLISHED VIA British Journal of Clinical Pharmacology. Author(s): Massi P, Solinas M, Cinquina V.