cancer
Many scientific studies report
cannabinoids exert a wide range of growth-inhibiting effects on cancer cells,
including:
- Stopping cells from dividing.
- Triggering cell
death, through a mechanism called
apoptosis.
- Preventing new blood vessels from growing into tumors
–a process termed angiogenesis.
- Reducing metastasization by
stopping cells from moving or invading neighboring tissue.
- Speeds up
internal 'waste disposal machine' – autophagy – which can lead to cell
death.
Conclusion: In 1975, Munson discovered that
cannabinoids suppress Lewis lung carcinoma cell growth. The mechanism of this
action was shown to be inhibition of DNA synthesis. Antiproliferative action on
some other cancer cells was also found.
Conclusion: This review will summarize the
anti-cancer properties of the cannabinoids.
Results emerging from preclinical studies
suggest cannabinoids elicit effects at different levels of cancer progression,
including inhibition of proliferation, neovascularization, invasion and
chemoresistance, induction of apoptosis and autophagy as well as enhancement of
tumour immune surveillance.
Cannabinoid compounds have been reported to
inhibit tumor growth and spreading in numerous rodent models. The underlying
mechanisms include induction of apoptosis, autophagy, and cell cycle arrest in tumor
cells as well as inhibition of tumor cell invasion and angiogenic features of
endothelial cells. In addition, cannabinoids have been shown to suppress
epithelial-to-mesenchymal transition
Conclusion: The results of the newest study
focused on the association between cannabinoids use and cancer risk showed no
significant association between increased cancer incidence and cannabinoids use
and it does not depend on the amount of used cannabis.
Conclusion: Control of the cellular
proliferation has become a focus of major attention as opening new therapeutic
possibilities for the use of cannabinoids as potential antitumor agents. The
capacity of endogenous and synthetic cannabinoids to
induce apoptosis of different tumoral cells in
culture and in vivo, the mechanism underlying and the potential therapeutic
applications are discussed in this review.
Conclusion: The development of
CB2-selective anticancer agents could be advantageous in light of
the unwanted central effects exerted by CB1 receptor ligands.
Conclusion: Cannabinoids are potential
anticancer agents.
Conclusion: The cannabinoid quinone HU-331 is
a highly specific inhibitor of topoisomerase II, compared with most known
anticancer quinones. It might represent a new potent anticancer drug.
Conclusion: These data lead us to consider
cannabidiol hydroxyquinone (HU-331) to have high potential as a new
antiangiogenic and anticancer drug.
Conclusion: These findings provide a novel
mechanism underlying the anti-invasive action of cannabidiol and imply its use
as a therapeutic option for the treatment of highly invasive cancers.
Conclusion: Phytocannabinoids and cannabis
extracts exert some of their pharmacological actions also by interacting with
TRPA1 and TRPM8 channels, with potential implications for the treatment of pain
and cancer.
Conclusion: These findings support a role for
p38 MAPK in CB2 receptor-induced apoptosis of human leukaemia
cells.
Conclusion: CB2 receptor activation
signals apoptosis via a ceramide-dependent
stimulation of the mitochondrial intrinsic pathway.
Conclusion: These findings constitute the
first evidence for an "astroprotective" role of cannabinoids: (i) cannabinoids
rescue primary astrocytes from C(2)-ceramide-induced apoptosis in a dose- and
time-dependent manner; (ii) triggering of this anti-apoptotic signal depends on
the phosphatidylinositol 3-kinase/protein kinase B pathway; (iii) ERK and its
downstream target p90 ribosomal S6 kinase might be also involved in the
protective effect of cannabinoids; and (iv) cannabinoids protect astrocytes
from the cytotoxic effects of focal C(2)-ceramide administration in
vivo.
tumor
Conclusion: Apart from their proapoptotic and
antiproliferative action, recent research has shown that cannabinoids may
likewise affect tumor cell angiogenesis, migration, invasion, adhesion, and
metastasization.
Conclusion: The potential use of cannabinoids
to retard tumor growth and spreading is even more appealing considering that
they show a good safety profile, regarding toxicity, and are already used in
cancer patients as palliatives to stimulate appetite and to prevent devastating
effects such as nausea, vomiting and pain.
Conclusion: The abundant expression and
distribution of CB2 receptors in glioblastoma and particularly
endothelial cells of glioblastoma indicate that impaired tumor growth in
presence of CB may be associated with CB2 activation. Selective
CB2 agonists might become important targets attenuating vascular
endothelial growth factor (VEGF) signalling and thereby diminishing
neoangiogenesis and glioblastoma growth.
Conclusion: Here, we describe the signaling
pathway that mediates cannabinoid-induced apoptosis of tumor cells.
Conclusion:
Cannabinoid-treated tumors showed an increased number of apoptotic cells. This
was accompanied by impairment of tumor vascularization, as determined by
altered blood vessel morphology and decreased
expression of proangiogenic factors
Conclusion: Data confirm the ability of
cannabinoids to induce cell death in different tumor models.
breast
These data suggest that anandamide blocks
human breast cancer cell
proliferation through CB1-like receptor-mediated inhibition of
endogenous prolactin action at the level of prolactin receptor.
Conclusion: CBD represents the first nontoxic
exogenous agent that can significantly decrease Id-1 expression in
metastatic breast cancer cells leading to
the down-regulation of tumor aggressiveness.
Cannabinoid receptor agonists are capable of
reducing proliferation and inducing apoptosis in diverse cancer cells such as
glioma, breast cancer,
and melanoma, we evaluated whether CB1 is a potential drug target in
rhabdomyosarcoma. Conclusion:
These results support the notion that cannabinoid receptor agonists could
represent a novel targeted approach for treatment of translocation-positive
rhabdomyosarcoma.
Conclusion: Anandamide was the first brain
metabolite shown to act as a ligand of "central" CB1 cannabinoid
receptors. Anandamide blocks
human
breast cancer cell proliferation through CB1-like
receptor-mediated inhibition of endogenous prolactin action at the level of
prolactin receptor.
Conclusion: Results obtained in a panel of
tumor cell lines clearly indicate that, of the five natural compounds tested,
cannabidiol is the most potent inhibitor of cancer cell growth (IC(50) between
6.0 and 10.6 microM), with significantly lower potency in noncancer cells.
Conclusion: The first report showing not only
that cannabinoids regulate JunD but, more generally, that JunD activation
reduces the proliferation of cancer cells, which points to a new target to
inhibit breast cancer
progression.
Conclusion: We found a correlation between
CB(2) expression and histologic grade of the tumors. There was also an
association between CB(2) expression and other markers of prognostic and
predictive value, such as estrogen receptor, progesterone receptor, and
ERBB2/HER-2 oncogene. Importantly, no significant CB(2) expression was detected
in nontumor breast tissue. Taken together, these data might set the bases for a
cannabinoid therapy for the management of breast
cancer.
The anticancer effects of the omega-3 long
chain polyunsaturated fatty acids
(LCPUFA), EPA and DHA may be due, at least in part, to conversion to their
respective endocannabinoid derivatives, eicosapentaenoyl-ethanolamine (EPEA)
and docosahexaenoyl-ethanolamine (DHEA). Attenuation of cell viability,
migration and invasion of malignant cells indicates a potential adjunct
nutritional therapeutic use of these LCPUFAs and/or their endocannabinoids in
treatment of breast
cancer.
Our results show that both
?9-tetrahydrocannabinol, the most abundant and potent cannabinoid in marijuana,
and JWH-133, a non-psychotropic CB2 receptor-selective agonist,
reduce tumor growth, tumor number, and the amount/severity of lung
metastases
Treatment with CBD significantly reduces
primary tumor mass as well as the size and number of lung metastatic foci in
two models of metastasis.
CBDA does not require CBs to exert its
anti-migration activity in MDA-MB-231 cells.
prostate
Conclusion: WIN-55,212-2 or other
non-habit-forming cannabinoid receptor agonists could be developed as novel
therapeutic agents for the treatment of prostate cancer.
Conclusion: This study defines the involvement
of CB(2)-mediated signalling in the in vivo and in vitro growth inhibition of
prostate cancer cells and suggests that CB(2) agonists have potential
therapeutic interest and deserve to be explored in the management of prostate
cancer.
Conclusion: THC caused apoptosis in a
dose-dependent manner. Morphological and biochemical changes induced by THC in
prostate PC-3 cells shared the characteristics of an apoptotic phenomenon.
We conclude that endocannabinoids are capable
of halting the growth of prostate cancer cells through activation of apoptotic
mechanisms.
The direct effects of phosphatase induction on
reduced phosphokinase protein expression was confounded by a parallel decrease
in most (total) kinase proteins.
Conclusion: Cannabinoids have shown antitumor
effects in many types of cancer models, CB2 may be a viable
therapeutic target for the treatment of anaplastic thyroid carcinoma.
Conclusion: New insights into the mechanism of
Met-F-AEA action, and could have significance in providing a basis for the
management of thyroid carcinoma.
Conclusion: Our results demonstrate that
Cannabinoids produce a significant cytotoxic effect via a receptor-independent
mechanism.
Conclusion: Results presented here show that
cannabinoids lead to apoptosis of pancreatic tumor cells via a CB(2) receptor
and de novo synthesized ceramide-dependent up-regulation of p8 and the
endoplasmic reticulum stress-related genes ATF-4 and TRB3.
Cannabinoids inhibit the glycolytic pathway:
To assess whether a restriction of the
energetic metabolism by cannabinoids could be responsible for the
enhancement of the cellular AMP level, we performed a targeted metabolomic
analysis.
Cannabinoids inhibit the Krebs cycle: To further examine the
involvement of the energetic metabolism in the induction of AMPK-mediated
autophagy by cannabinoids, we analysed the critical metabolites of the Krebs
cycle.
Conclusion: The cytotoxic effect of a
cannabinoid is enhanced by modulation of ceramide metabolism.
Conclusion: Induction of apoptosis in
mantle cell lymphoma.
Conclusion: Cannabinoids induce growth
inhibition and apoptosis in mantle cell lymphoma.
Conclusion: Cannabinoid receptor ligands will
have efficiency in reducing tumor burden in malignant lymphoma overexpressing
CB1 and CB2.
Conclusion: Culture of primary acute
lymphoblastic leukemia
cells with THC in vitro reduced cell viability and induced
apoptosis.
glioma
Conclusion: Cannabinoids seem to be selective
antitumoral compounds, as they kill glioma cells, but not their non-transformed
astroglial counterparts.
Cannabinoids-endocannabinoids exert
anti-inflammatory, anti-proliferative, anti-invasive, anti-metastatic and
pro-apoptotic effects in different cancer types, both in vitro and in vivo in
animal models, after local or systemic administration.
Conclusion: A pilot clinical trial on patients
with glioblastoma multiforme demonstrated their good safety profile together
and remarkable antitumor effects.
Conclusion: In contrast with their role in
THC-mediated death, both CB1 and CB2 partially protected
glioma against Arachidonylethanolamide-induced apoptosis.
Conclusion: This study defines COX-2 as a
hitherto unknown target by which a cannabinoid induces apoptotic death of
glioma cells.
Conclusion: The nonpsychoactive CBD was able
to produce a significant antitumor activity both in vitro and in vivo, thus
suggesting a possible
application of CBD as an antineoplastic agent.
Conclusion: TIMP-1 down-regulation may be a
hallmark of cannabinoid-induced inhibition of glioma progression.
Conclusion: Results demonstrate that
cannabinoids target glioma stem-like cells,
promote their
differentiation, and inhibit gliomagenesis, thus giving further support to
their potential use in the management of malignant gliomas.
Conclusion:
THC can promote the autophagic
death of human cancer cells and provide evidence that cannabinoid
administration may be an effective therapeutic strategy for targeting human
cancers.
Conclusion: Cannabinoid-induced inhibition of
MMP-2 expression and cell invasion was prevented by blocking ceramide
biosynthesis and by knocking-down the expression of the stress protein p8.
Conclusion: THC-induced apoptosis in glioma
C6.9 cells relys on a CBI receptor-independent stimulation of sphingomyelin
breakdown.
Conclusion: Cannabinoids were shown to induce
apoptosis of glioma cells in vitro and tumor regression in vivo.
Conclusion: Δ9-THC is shown to
significantly affect viability of GBM cells via a mechanism that appears to
elicit G(1) arrest due to downregulation of E2F1 and Cyclin A.
Conclusion: Tumors growing in the brains of
mice were drastically slowed down when THC/CBD was used with irradiation.
The present investigation confirms the
antiproliferative and antiinvasive effects of CBD in U87-MG cells.
colon
Estrogenic induction of cannabinoid
CB1 receptor in human colon cancer cell lines.
Conclusion: The CB1 receptor can be
considered an estrogen-responsive gene.
Cannabinoid receptor activation induces
apoptosis through tumor necrosis factor alpha-mediated ceramide de novo
synthesis in colon cancer cells.
Conclusion: The present study shows that
either CB1 or CB2 receptor activation induces apoptosis
through ceramide de novo synthesis in colon cancer cells.
The cannabinoid
Δ9-tetrahydrocannabinol inhibits RAS-MAPK and PI3K-AKT survival
signalling and induces BAD-mediated apoptosis in colorectal cancer cells.
Conclusion: These data suggest an important
role for CB1 receptors and BAD in the regulation of apoptosis in
colorectal cancer cells. The use of THC, or selective targeting of the
CB1 receptor, may represent a novel strategy for colorectal cancer
therapy.
Conclusions: The present study shows that
either CB1 or CB2 receptor activation induces apoptosis
through ceramide de novo synthesis in colon cancer cells. Our data unveiled,
for the first time, that TNF-α acts as a link between cannabinoid receptor
activation and ceramide production.
Results: CBD BDS and CBD reduced cell
proliferation in tumoral, but not in healthy, cells.
leukemia
Δ9-tetrahydrocannabinol-induced
apoptosis in Jurkat leukemia
T lymphocytes is
regulated by translocation of Bad to mitochondria.
Conclusion: Raf-1/MEK/ERK/RSK-mediated Bad
translocation played a critical role in THC-induced apoptosis in Jurkat
cells.
Conclusion: The results from this study reveal
that cannabidiol, acting through CB2 and regulation of Nox4 and
p22(phox) expression, may be a novel and highly selective treatment for
leukemia.
Conclusion: 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.
Conclusion: 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
mitogen-activated protein kinase (MAPK) signal transduction pathways.
cervical
Conclusion: A role of COX-2 and PPARgamma in
MA-induced apoptosis was confirmed in another human cervical cancer cell line
(C33A) and in human lung
carcinoma cells (A549).
Conclusion: Using Matrigel invasion assays we
found a cannabidiol-driven impaired invasion of human cervical cancer (HeLa,
C33A) and human lung cancer cells (A549) that was reversed by antagonists to
both CB(1) and CB(2) receptors as well as to transient receptor potential
vanilloid 1 (TRPV1). These findings provide a novel mechanism underlying the
anti-invasive action of cannabidiol and imply its use as a therapeutic option
for the treatment of highly invasive cancers.
Women with gynecologic cancer report a strong
interest in the use of non-prescription cannabis products for management of
cancer-related symptoms. Practitioners in the field of gynecologic oncology
should be aware of the frequency of use of non-prescription cannabis amongst
their patients as well as the growing desire for guidance about the use of
cannabis derivatives. A substantial number of patients report decreased
reliance on opioids when using cannabis derivatives for pain control.
Conclusion: Both thymocytes and EL-4 thymoma
cells are susceptible to CBD-induced apoptosis.
Conclusion: Thymocytes and splenocytes exposed
to THC in vivo exhibited apoptosis upon in vitro culture. Together, these
results suggest that in vivo exposure to THC can lead to significant
suppression of the immune response by induction of apoptosis.
Conclusion: THC retards
cholangiocarcinoma cell growth
and metastasis.
Conclusion: Cannabinoid antiproliferative
action on melanoma cells was due, at least in part, to cell cycle arrest at the
G1-S transition via inhibition of the prosurvival protein Akt and
hypophosphorylation of the pRb retinoblastoma protein tumor suppressor.
Conclusion: Previous studies have indicated
the antitumoral effect of human melanocytes, human melanoma cell lines
expressing CB1 receptor (CB1), and of the peritumoral
administration of endocannabinoids. Our studies revealed that systemic
administration of a stable CB1 agonist, ACEA, into SCID mice
specifically inhibited liver colonization of human melanoma cells.
Conclusion: Although the global incidence of
cutaneous melanoma is increasing, survival rates for patients with metastatic
disease remain <10%. our findings suggest that THC activates noncanonical
autophagy-mediated apoptosis of melanoma cells, suggesting that cytotoxic
autophagy induction with Sativex warrants clinical evaluation for metastatic
disease.
Our findings suggest that phytocannabinoids
and cannabis extracts exert some of their pharmacological actions also by
interacting with TRPA1 and TRPM8 channels, with potential implications for the
treatment of pain and cancer.
astrocytomas
Conclusion: The high expression level of CB(1)
and CB(2) receptors commonly found in malignant astrocytomas precludes the use
of cannabinoids as therapeutics, unless AKT is concomitantly inhibited, or
cannabinoids are applied at concentrations that bypass CB(1) and CB(2)
receptors, yet still activate ERK1/2.
lung
Conclusion:Our pooled results showed no
significant association between the intensity, duration, or cumulative
consumption of cannabis smoke and the risk of
lung cancer overall or in never
smokers.
Δ9-Tetrahydrocannabinol
inhibits epithelial growth factor-induced lung cancer cell migration in vitro
as well as its growth and metastasis in vivo.
Conclusion: There was significant inhibition
of the subcutaneous tumor growth and lung metastasis of A549 cells in
THC-treated animals as compared to vehicle-treated controls. Tumor samples from
THC-treated animals revealed antiproliferative and antiangiogenic effects of
THC.
Conclusion: Our data indicate that
cannabinoids induce ICAM-1, thereby conferring TIMP-1 induction and subsequent
decreased cancer cell invasiveness |
