Enhancement of androgen receptor expression induced by (<i>R</i>)‐methanandamide in prostate LNCaP cells

Sánchez, María del Mar; Sánchez, Ana M.; Ruiz, Lı́dia; Díaz‐Laviada, Inés

doi:10.1016/s0014-5793(03)01349-8

Cited by 53 publications

(49 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…2B). Only in the case of human DU-145 prostate carcinoma cells, plant cannabinoids induced a stimulatory effect on cancer growth at the lowest doses tested and an inhibitory effect only at the highest concentration tested (25 M) (as also found by Sanchez et al, 2003 in another prostate carcinoma cell line). In this case, however, the cannabidiolrich extract lacked the pro-proliferative effect even at the lowest concentration tested of 2 M (Fig.…”

Section: Resultssupporting

confidence: 58%

Antitumor Activity of Plant Cannabinoids with Emphasis on the Effect of Cannabidiol on Human Breast Carcinoma

Ligresti

Moriello²,

Starowicz³

et al. 2006

J Pharmacol Exp Ther

470

449

View full text Add to dashboard Cite

⌬9 -Tetrahydrocannabinol (THC) exhibits antitumor effects on various cancer cell types, but its use in chemotherapy is limited by its psychotropic activity. We investigated the antitumor activities of other plant cannabinoids, i.e., cannabidiol, cannabigerol, cannabichromene, cannabidiol acid and THC acid, and assessed whether there is any advantage in using Cannabis extracts (enriched in either cannabidiol or THC) over pure cannabinoids. 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 M), with significantly lower potency in noncancer cells. The cannabidiol-rich extract was equipotent to cannabidiol, whereas cannabigerol and cannabichromene followed in the rank of potency. Both cannabidiol and the cannabidiol-rich extract inhibited the growth of xenograft tumors obtained by s.c. injection into athymic mice of human MDA-MB-231 breast carcinoma or rat v-K-ras-transformed thyroid epithelial cells and reduced lung metastases deriving from intrapaw injection of MDA-MB-231 cells. Judging from several experiments on its possible cellular and molecular mechanisms of action, we propose that cannabidiol lacks a unique mode of action in the cell lines investigated. At least for MDA-MB-231 cells, however, our experiments indicate that cannabidiol effect is due to its capability of inducing apoptosis via: direct or indirect activation of cannabinoid CB 2 and vanilloid transient receptor potential vanilloid type-1 receptors and cannabinoid/vanilloid receptor-independent elevation of intracellular Ca 2ϩ and reactive oxygen species. Our data support the further testing of cannabidiol and cannabidiol-rich extracts for the potential treatment of cancer.The therapeutic properties of the hemp plant, Cannabis sativa, have been known since antiquity, but the recreational use of its euphoric and other psychoactive effects has restricted for a long time research on its possible pharmaceutical application. The isolation of ⌬ 9 -tetrahydrocannabinol (THC), the main psychoactive component of Cannabis (Gaoni and Mechoulam, 1964), opened the way to further investigations. After the discovery of the two specific molecular targets for THC, CB 1 , and CB 2 (for review, see Pertwee, 1997), it became clear that most of the effects of marijuana in the brain and peripheral tissues were due to activation of these two G-protein-coupled cannabinoid receptors. However, evidence is also accumulating that some pharmacological effects of marijuana are due to Cannabis components different from THC. Indeed, C. sativa contains at least 400 chemical components, of which 66 have been identified to belong to the class of the cannabinoids (Pertwee, 1997).To date, cannabinoids have been successfully used in the treatment of nausea and vomiting (for review, see Robson, This study was supported by GW Pharmaceuticals (research grant to V.D.M.).Article, publication date, and citation information can be found...

show abstract

Section: Resultssupporting

confidence: 58%

Antitumor Activity of Plant Cannabinoids with Emphasis on the Effect of Cannabidiol on Human Breast Carcinoma

Ligresti

Moriello²,

Starowicz³

et al. 2006

J Pharmacol Exp Ther

470

449

View full text Add to dashboard Cite

show abstract

“…Later studies showed an increased expression of both CB 1 and CB 2 receptors in cultured prostate cancer cells when compared with normal prostate cells. Moreover, treatment of prostate cancer cells with WIN-55,212-2 resulted in a dose and time dependent decrease in cell viability, increased apoptosis along with decrease in androgen receptor protein expression, PSA expression, and secreted PSA, suggesting that cannabinoids should be considered as agents for the management of prostate cancer Sanchez et al, 2003;Sarfaraz et al, 2005). It was also found that a high level of CB 1 receptor immunoreactivity (CB 1 IR) in prostate cancer tissues is associated with the severity and outcome of the disease (Chung et al, 2009).…”

Section: Cannabinoids and Reproductive System Cancermentioning

confidence: 99%

Cannabinoid pharmacology in cancer research: A new hope for cancer patients?

Javid

Phillips

Afshinjavid

et al. 2016

European Journal of Pharmacology

View full text Add to dashboard Cite

Cannabinoids have been used for many centuries to ease pain and in the past decade, the endocannabinoid system has been implicated in a number of pathophysiological conditions, such as mood and anxiety disorders, movement disorders such as Parkinson's and Huntington's disease, neuropathic pain, multiple sclerosis, spinal cord injury, atherosclerosis, myocardial infarction, stroke, hypertension, glaucoma, obesity, and osteoporosis. Several studies have demonstrated that cannabinoids also have anti-cancer activity and as cannabinoids are usually well tolerated and do not produce the typical toxic effects of conventional chemotherapies, there is considerable merit in the development of cannabinoids as potential anticancer therapies. Whilst the presence of psychoactive effects of cannabinoids could prevent any progress in this field, recent studies have shown the value of the non-psychoactive components of cannabinoids in activating apoptotic pathways, inducing anti-proliferative and anti-angiogenic effects. The aforementioned effects are suggested to be through pathways such as ERK, Akt, mitogen-activated protein kinase (MAPK) pathways, phosphoinositide 3-kinase (PI3K) pathways and hypoxia inducible factor 1 (HIF1), all of which are important contributors to the hallmarks of cancer. Many important questions still remain unanswered or are poorly addressed thus necessitating further research at basic pre-clinical and clinical levels. In this review, we address these issues with a view to identifying the key challenges that future research needs to address.

show abstract

“…HU 210 and AEA produced increased calcein fluorescence in the nanomolar range, whereas micromolar concentrations produced a "threshold"-like profile with little or no toxicity at 1 µM and maximal toxicity in the range of 3-30 µM. This prompted further investigation into bimodal effects on P19 cell viability since it has been shown that CBs have mitogenic effects on prostate LNCaP cells at submicromolar concentrations (Sanchez et al 2003) and endocannabinoids have been shown to promote cell proliferation and neurosphere generation in a CB1 dependent manner (Aguado et al 2005). However, when the apparent stimulatory effects of some of the CBs on the fluorescence of calcein in P19 cells were re-examined by using the CyQUANT proliferation kit, the [3H]-thymidine incorporation assay, and by analysis of cell cycle profile using PI-directed FACScan, it could be concluded that the increased fluorescence in the submicromolar range is not due to increased cellular proliferation.…”

Section: Discussionmentioning

confidence: 99%

Effects of cannabinoids and related fatty acids upon the viability of P19 embryonal carcinoma cells

et al. 2013

View full text Add to dashboard Cite

Plym Forshell, L. et al. (2013) Effects of cannabinoids and related fatty acids upon the viability of P19 embryonal carcinoma cells. Toxicology, 87(11): 1939Toxicology, 87(11): -1951 http://dx.doi.org/10.1007/s00204-013-1051-3 Archives ofAccess to the published version may require subscription. Abstract Compounds acting on the cannabinoid (CB) receptors are involved in the control of cell fate, and there is an emerging consensus that CBs have anticancer effects. However, the CB-mediated effects are contradictory since some studies suggest stimulatory effects on cancer cell proliferation, and CBs have been shown to stimulate both proliferation and differentiation of other mitotic cells such as stem and progenitor cells. In this study, the concentration-dependent effects of synthetic and endogenous CBs on the viability of mouse P19 embryonal carcinoma (EC) cells have been examined by using fluorescence assays of cell membrane integrity, cell proliferation, oxidative stress, and detection of apoptosis and necrosis. All compounds examined produced a concentrationdependent decrease in cell viability in the micromolar range, with the potent CB receptor agonist HU 210 and the enantiomer HU 211(with no CB receptor activity) being the most potent compounds examined with apparent IC 50 values of 1 µM and 0.6 µM, respectively. The endogenous CB anandamide showed similar potency and efficacy as structurally related polyunsaturated fatty acids with no reported activity at the CB receptors. The rapid (within hours) decrease in cell viability induced by the examined CBs suggests cytocidal rather than antiproliferative effects, and is dependent on the plating cell population density with the highest toxicity around 100 cells/mm 2 . The CB-induced cytotoxicity, that appears to involve CB receptors and the sphingomyelin-ceramide pathway, is a mixture of both apoptosis and necrosis that can be blocked by the antioxidants α-tocopherol and Nacetylcysteine. In conclusion, both synthetic and endogenous CBs, produce seemingly unspecific cytotoxic effects in the P19 EC cells.

show abstract

Enhancement of androgen receptor expression induced by (R)‐methanandamide in prostate LNCaP cells

Cited by 53 publications

References 37 publications

Antitumor Activity of Plant Cannabinoids with Emphasis on the Effect of Cannabidiol on Human Breast Carcinoma

Antitumor Activity of Plant Cannabinoids with Emphasis on the Effect of Cannabidiol on Human Breast Carcinoma

Cannabinoid pharmacology in cancer research: A new hope for cancer patients?

Effects of cannabinoids and related fatty acids upon the viability of P19 embryonal carcinoma cells

Contact Info

Product

Resources

About