Tag Archives: apoptosis

Cannabis: A Prehistoric Remedy for the Deficits of Existing and Emerging Anticancer Therapies

Posted on by
Reply

“Cannabis has been used medicinally for centuries and numerous species of this genus are undoubtedly amongst the primeval plant remedies known to humans.

Cannabis sativa in particular is the most reported species, due to its substantial therapeutic implications that are owed to the presence of chemically and pharmacologically diverse cannabinoids.

These compounds have long been used for the palliative treatment of cancer.

Recent advancements in receptor pharmacology research have led to the identification of cannabinoids as effective antitumor agents.

This property is accredited for their ability to induce apoptosis, suppress proliferative cell signalling pathways and promote cell growth inhibition.

Evolving lines of evidence suggest that cannabinoid analogues, as well as their receptor agonists, may offer a novel strategy to treat various forms of cancer.

This review summarizes the historical perspective of C. sativa, its potential mechanism of action, and pharmacokinetic and pharmacodynamic aspects of cannabinoids, with special emphasis on their anticancer potentials.”

http://www.xiahepublishing.com/ArticleFullText.aspx?sid=2&jid=3&id=10.14218%2FJERP.2017.00012

Cannabis products.

“Cannabis products. First row, left to right: Indian, Lebanese, Turkish and Pakistani hashish. Second row, left to right: Swiss hashish, Zairean marijuana, Swiss marijuana, Moroccan hash oil.”

Novel therapeutic applications of cannabinoids in cancer disease

Posted on by
Reply

oatext

“The present review shows that cannabinoids exert their anti-cancer effects in a number of ways and in a variety of tissues.

The endocannabinoid system is an almost ubiquitous signalling system involved in the control of cell fate. Recent studies have investigated the possibility that drugs targeting the endocannabinoid system might be used to retard or block cancer growth.

The endocannabinoids have been shown to inhibit the growth of tumour cells in culture and animal models by modulating key cell signalling pathways. Therefore, the present review indicated that cannabinoids exert their anti-cancer effects in a number of ways and in a variety of tissues.

  • Triggering cell death, through a mechanism called apoptosis
  • Stopping cells from dividing
  • Preventing new blood vessels from growing into tumours
  • Reducing the chances of cancer cells spreading through the body, by stopping cells from moving or invading neighbouring tissue
  • Speeding up the cell’s internal ‘waste disposal machine’ – a process known as autophagy – which can lead to cell death

Furthermore, the novel therapeutic application of cannabinoids in cancer disease, described here, strongly support the idea that cannabinoids may induce benefical effect in cancer treatment.”

http://www.oatext.com/novel-therapeutic-applications-of-cannabinoids-in-cancer-disease.php

Targeting cannabinoid receptors in gastrointestinal cancers for therapeutic uses: current status and future perspectives

Posted on by
Reply

Publication Cover

“A number of studies have consistently shown that cannabinoids are able to prevent or reduce carcinogenesis in different animal models of colon cancer.

Cannabinoids, via CB1 and possibly CB2 receptors, suppress proliferation and migration and stimulate apoptosis in colorectal cancer cells.

Convincing scientific evidence suggests that cannabinoids, in addition to their well-known use in palliative care in oncology (e.g. improvement of appetite, attenuation of nausea associated to antitumoral medicines, alleviation of moderate neuropathic pain) can reduce, via antiproliferative and proapoptotic as well as by inhibiting angiogenesis, invasion and metastasis or by attenuating inflammation, the growth of cancer cells and hinder the development of experimental colon carcinogenesis in vivo.”

https://www.tandfonline.com/doi/full/10.1080/17474124.2017.1367663?src=recsys

Cannabinoids as a Promising Therapeutic Approach for the Treatment of Glioblastoma Multiforme: A Literature Review

Posted on by
Reply

Page Header

“Gliobalstoma multiforme (GBM) or grade 4 astrocytoma is the most malignant form of primary brain tumor. Treatment of glioblastoma is difficult despite of surgery, radiotherapy and chemotherapy. Patients with glioblastoma survive for less than 12 months.

Considering to biology function of glioblastoma, researchers have recently offered new therapeutic approaches such as cannabinoid therapy for glioblastoma.

Cannabinoids are active compounds of Cannabis sativa that operate in the body similar to endogenous canabinoids –the endocannabinoids- through cell surface receptors.

It is interesting that cannabinoids could exert a wide spectrum from antiproliferative effects in condition of the cell culture, animal models of glioblastoma and clinical trials.

As a result, Cannabinoids seem to modulate intracellular signaling pathways and the endoplasmic reticulum stress response in glioma cells.

Those play antitumoral effects through apoptosis induction and inhibition of glioblastoma angiogenesis.

The goal of this study was to discuss cannabinoid therapy and also what cellular mechanisms are involved in the tumoricidal effect of the cannabinoids.

In this review article, we will focus on cannabinoids, their receptor dependent functional roles against glioblastoma acccording to growth, angiogenesis, metastasis, and future purposes in exploring new possible therapeutic opportunities.”

http://journals.sbmu.ac.ir/Neuroscience/article/view/13655

Cannabinoids in Glioblastoma Therapy: New Applications for Old Drugs

Posted on by
Reply

Image result for frontiers in molecular neuroscience

“Glioblastoma (GBM) is the most malignant brain tumor and one of the deadliest types of solid cancer overall. Despite aggressive therapeutic approaches consisting of maximum safe surgical resection and radio-chemotherapy, more than 95% of GBM patients die within 5 years after diagnosis. Thus, there is still an urgent need to develop novel therapeutic strategies against this disease.

Accumulating evidence indicates that cannabinoids have potent anti-tumor functions and might be used successfully in the treatment of GBM.

This review article summarizes the latest findings on the molecular effects of cannabinoids on GBM, both in vitro and in (pre-) clinical studies in animal models and patients.

The therapeutic effect of cannabinoids is based on reduction of tumor growth via inhibition of tumor proliferation and angiogenesis but also via induction of tumor cell death. Additionally, cannabinoids were shown to inhibit the invasiveness and the stem cell-like properties of GBM tumors. Recent phase II clinical trials indicated positive results regarding the survival of GBM patients upon cannabinoid treatment.

Apart from a direct killing effect on tumor cells, cannabinoids can also induce cell cycle arrest thereby inhibiting tumor cell proliferation.

In conclusion, cannabinoids show promising anti-neoplastic functions in GBM by targeting multiple cancer hallmarks such as resistance to programmed cell death, neoangiogenesis, tissue invasion or stem cell-induced replicative immortality.

The effects of cannabinoids can be potentially enhanced by combination of different cannabinoids with each other or with chemotherapeutic agents. This requires, however, a detailed understanding of cannabinoid-induced molecular mechanisms and pharmacological effects.

Ultimately, these findings might foster the development of improved therapeutic strategies against GBM and, perhaps, other diseases of the nervous system as well.”

https://www.frontiersin.org/articles/10.3389/fnmol.2018.00159/full

“Accumulating evidence indicates that cannabinoids have potent anti-tumor functions and might be used successfully in the treatment of GBM.”  https://www.ncbi.nlm.nih.gov/pubmed/29867351

Endocannabinoid system and anticancer properties of cannabinoids

Posted on by
Reply

Folia Biologica et Oecologica

“Cannabinoids impact human body by binding to cannabinoids receptors (CB1 and CB2).

The two main phytocannabinoids are Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD).

THC interacts with CB1 receptors occurring in central nervous system and is responsible for psychoactive properties of marijuana. CBD has low affinity to CB1 receptor, has no psychoactive characteristics and its medical applications can be wider.

CB receptors are part of a complex machinery involved in regulation of many physiological processes – endocannabinoid system.

Cannabinoids have found some applications in palliative medicine, but there are many reports concerning their anticancer affects.

Agonists of CB1 receptors stimulate accumulation of ceramides in cancer cells, stress of endoplasmic reticulum (ER stress) and, in turn, apoptosis. Effects of cannabinoids showing low affinity to CB receptors is mediated probably by induction of reactive oxygen species production.

Knowledge of antitumor activity of cannabinoids is still based only on preclinical studies and there is a necessity to conduct more experiments to assess the real potential of these compounds.”

https://content.sciendo.com/view/journals/fobio/12/1/article-p11.xml

Effects of CB2 and TRPV1 receptors’ stimulation in pediatric acute T-lymphoblastic leukemia

Posted on by
Reply

Related image

“T-Acute Lymphoblastic Leukemia (T-ALL) is less frequent than B-ALL, but it has poorer outcome. For this reason new therapeutic approaches are needed to treat this malignancy.

The Endocannabinoid/Endovanilloid (EC/EV) system has been proposed as possible target to treat several malignancies, including lymphoblastic diseases. The EC/EV system is composed of two G-Protein Coupled Receptors (CB1 and CB2), the Transient Potential Vanilloid 1 (TRPV1) channel, their endogenous and exogenous ligands and enzymes. CB1 is expressed mainly in central nervous system while CB2 predominantly on immune and peripheral cells, therefore we chose to selectively stimulate CB2 and TRPV1.

We treated T-ALL lymphoblasts derived from 4 patients and Jurkat cells with a selective agonist at CB2 receptor: JWH-133 [100 nM] and an agonist at TRPV1 calcium channel: RTX [5 uM] at 6, 12 and 24 hours. We analyzed the effect on apoptosis and Cell Cycle Progression by a cytofluorimetric assays and evaluated the expression level of several target genes (Caspase 3, Bax, Bcl-2, AKT, ERK, PTEN, Notch-1, CDK2, p53) involved in cell survival and apoptosis, by Real-Time PCR and Western Blotting.

We observed a pro-apoptotic, anti-proliferative effect of these compounds in both primary lymphoblasts obtained from patients with T-ALL and in Jurkat cell line. Our results show that both CB2 stimulation and TRPV1 activation, can increase the apoptosis in vitro, interfere with cell cycle progression and reduce cell proliferation, indicating that a new therapeutic approach to T-cell ALL might be possible by modulating CB2 and TRPV1 receptors.”

http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=25052

Enhancing the Therapeutic Efficacy of Cancer Treatment With Cannabinoids

Posted on by
Reply

Image result for frontiers in oncology

“Many in vitro and in vivo studies have reported on the antitumorigenic effects of plant-derived cannabinoids (CBDs) and their synthetic analogs, including effects in inducing apoptosis and inhibiting tumor cell growth and metastasis.

Over the years, many in vitro and in vivo studies have shown the antineoplastic effects of cannabinoids (CBDs), with reports advocating for investigations of combination therapy approaches that could better leverage these effects in clinical translation.

This study explores the potential of combination approaches employing CBDs with radiotherapy (RT) or smart biomaterials toward enhancing therapeutic efficacy during treatment of pancreatic and lung cancers. In in vitro studies, clonogenic assay results showed greater effective tumor cell killing, when combining CBDs and RT. Meanwhile, in vivo study results revealed major increase in survival when employing smart biomaterials for sustained delivery of CBDs to tumor cells. The significance of these findings, considerations for further research, and viable roadmap to clinical translation are discussed.

The advantage of combining CBDs with other therapies is that this may allow simultaneous targeting of tumor progression at different levels, while minimizing toxicities for these therapies relative to toxicities from higher doses when used as monotherapies.”
https://www.ncbi.nlm.nih.gov/pubmed/29740535
https://www.frontiersin.org/articles/10.3389/fonc.2018.00114/full

“Cannabis Science Announces the Second Frontiers Peer-Reviewed Publication of its Research Results on the Use of Cannabinoids in the Treatment of Cancers”  https://globenewswire.com/news-release/2018/05/01/1493854/0/en/Cannabis-Science-Announces-the-Second-Frontiers-Peer-Reviewed-Publication-of-its-Research-Results-on-the-Use-of-Cannabinoids-in-the-Treatment-of-Cancers.html

The current state and future perspectives of cannabinoids in cancer biology.

Posted on by
Reply

Cancer Medicine

“To date, cannabinoids have been allowed in the palliative medicine due to their analgesic and antiemetic effects, but increasing number of preclinical studies indicates their anticancer properties. Cannabinoids exhibit their action by a modulation of the signaling pathways crucial in the control of cell proliferation and survival. Many in vitro and in vivo experiments have shown that cannabinoids inhibit proliferation of cancer cells, stimulate autophagy and apoptosis, and have also a potential to inhibit angiogenesis and metastasis. In this review, we present an actual state of knowledge regarding molecular mechanisms of cannabinoids’ anticancer action, but we discuss also aspects that are still not fully understood such as the role of the endocannabinoid system in a carcinogenesis, the impact of cannabinoids on the immune system in the context of cancer development, or the cases of a stimulation of cancer cells’ proliferation by cannabinoids. The review includes also a summary of currently ongoing clinical trials evaluating the safety and efficacy of cannabinoids as anticancer agents.”

https://www.ncbi.nlm.nih.gov/pubmed/29473338

http://onlinelibrary.wiley.com/doi/10.1002/cam4.1312/abstract

Cannabinoid-induced cell death in endometrial cancer cells: involvement of TRPV1 receptors in apoptosis.

Posted on by
Reply

Journal of Physiology and Biochemistry

“Among a variety of phytocannabinoids, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are the most promising therapeutic compounds. Besides the well-known palliative effects in cancer patients, cannabinoids have been shown to inhibit in vitro growth of tumor cells.

Likewise, the major endocannabinoids (eCBs), anandamide (AEA) and 2-arachidonoylglycerol (2-AG), induce tumor cell death.

The purpose of the present study was to characterize cannabinoid elements and evaluate the effect of cannabinoids in endometrial cancer cell viability.

These data indicate that cannabinoids modulate endometrial cancer cell death.

Selective targeting of TPRV1 by AEA, CBD, or other stable analogues may be an attractive research area for the treatment of estrogen-dependent endometrial carcinoma.

Our data further support the evaluation of CBD and CBD-rich extracts for the potential treatment of endometrial cancer, particularly, that has become non-responsive to common therapies.”

https://www.ncbi.nlm.nih.gov/pubmed/29441458

https://link.springer.com/article/10.1007%2Fs13105-018-0611-7