Anti-proliferative and cytotoxic effect of cannabidiol on human cancer cell lines in presence of serum

 BMC Research Notes | Home page“Objective: Cannabinoids are able to reduce tumor growth in xenograft models, but their therapeutic potential as anti-cancer drugs in humans is unclear yet. In vitro studies of the effect of cannabinoids on cancer cells are often carried out in absence of serum or in low serum concentration (i.e. 0.5% serum), conditions that limit cellular growth and therefore can increase the response of cells to additional challenges such as the presence of cannabinoids. However, the tumor microenvironment can be teaming with growth factors. In this study we assessed the viability and proliferation of cancer cells treated with cannabidiol in presence of a serum concentration that commonly sustains cell growth (10% serum).

Results: The results show that cannabidiol exerts a markedly different effect on the viability of the human HT-29 cancer cell line when cultured in presence of 0.5% serum in comparison to 10% serum, displaying a cytotoxic effect only in the former situation. In presence of 10% serum, no inhibitory effect of cannabidiol on DNA replication of HT-29 cells was detected, and a weak inhibition was observed for other cancer cell lines. These results indicate that the effect of cannabidiol is cell context-dependent being modulated by the presence of growth factors.”

https://pubmed.ncbi.nlm.nih.gov/32819436/

“The cannabis plant has a therapeutic potential to treat a wide range of diseases, including cancer.”

https://bmcresnotes.biomedcentral.com/articles/10.1186/s13104-020-05229-5

Roles of Cannabinoids in Melanoma: Evidence from In Vivo Studies

ijms-logo“Melanoma is the fourth most common type of cancer diagnosed in Australians after breast, prostate, and colorectal cancers. While there has been substantial progress in the treatment of cancer in general, malignant melanoma, in particular, is resistant to existing medical therapies requiring an urgent need to develop effective treatments with lesser side effects.

Several studies have shown that “cannabinoids”, the major compounds of the Cannabis sativaL. plant, can reduce cell proliferation and induce apoptosis in melanoma cells.

Despite prohibited use of Cannabis in most parts of the world, in recent years there have been renewed interests in exploiting the beneficial health effects of the Cannabis plant-derived compounds. Therefore, the aim of this study was in the first instance to review the evidence from in vivo studies on the effects of cannabinoids on melanoma.

The findings revealed cannabinoids, individually or combined, reduced tumor growth and promoted apoptosis and autophagy in melanoma cells.

Further preclinical and animal studies are required to determine the underlying mechanisms of cannabinoids-mediated inhibition of cancer-signaling pathways. Well-structured, randomized clinical studies on cannabinoid use in melanoma patients would also be required prior to cannabinoids becoming a viable and recognized therapeutic option for melanoma treatment in patients.”

https://pubmed.ncbi.nlm.nih.gov/32839414/

https://www.mdpi.com/1422-0067/21/17/6040

Cannabinoid Effects on Experimental Colorectal Cancer Models Reduce Aberrant Crypt Foci (ACF) and Tumor Volume: A Systematic Review

See the source image “Colorectal cancer represents a heavy burden for health systems worldwide, being the third most common cancer worldwide. Despite the breakthroughs in medicine, current chemotherapeutic options continue to have important side effects and may not be effective in preventing disease progression.

Cannabinoids might be substances with possible therapeutic potential for cancer because they can attenuate the side effects of chemotherapy and have antiproliferative and antimetastatic effects.

We aim to determine, through a systematic review of experimental studies performed on animal CRC models, if cannabinoids can reduce the formation of preneoplastic lesions (aberrant crypt foci), number, and volume of neoplastic lesions.

Results: Eight in vivo experimental studies were included in the analysis after the full-text evaluation. Seven studies were azoxymethane (AOM) colorectal cancer models, and four studies were xenograft models. Cannabidiol botanical substance (CBD BS) and rimonabant achieved high aberrant crypt foci (ACF) reduction (86% and 75.4%, respectively). Cannabigerol, O-1602, and URB-602 demonstrated a high capacity for tumor volume reduction. Induction of apoptosis, interaction with cell survival, growth pathways, and angiogenesis inhibition were the mechanisms extracted from the studies that explain cannabinoids’ actions on CRC.

Conclusions: Cannabinoids have incredible potential as antineoplastic agents as experimental models demonstrate that they can reduce tumor volume and ACF formation. It is crucial to conduct more experimental studies to understand the pharmacology of cannabinoids in CRC better.”

https://pubmed.ncbi.nlm.nih.gov/32765628/

“Current literature findings demonstrate that cannabinoids might have potential as antineoplastic agents because they can reduce tumor volume and ACF formation.”

https://www.hindawi.com/journals/ecam/2020/2371527/

The Effects of Cannabidiol and Prognostic Role of TRPV2 in Human Endometrial Cancer

ijms-logo“Several studies support, both in vitro and in vivo, the anti-cancer effects of cannabidiol (CBD), a transient receptor potential vanilloid 2 (TRPV2) ligand. TRPV2, often dysregulated in tumors, is associated with altered cell proliferation and aggressiveness.

Endometrial cancer (EC) is historically divided in type I endometrioid EC and type II non-endometrioid EC, associated with poor prognosis. Treatment options with chemotherapy and combinations with radiation showed only limited efficacy. Since no data are reported concerning TRPV2 expression as well as CBD potential effects in EC, the aim of this study was to evaluate the expression of TRPV2 in biopsies and cell lines as well as the effects of CBD in in vitro models. Overall survival (OS), progression-free survival (PFS), cell viability, migration, and chemo-resistance have been evaluated.

Results show that TRPV2 expression increased with the malignancy of the cancer tissue and correlated with shorter PFS (p = 0.0224). Moreover, in vitro TRPV2 over-expression in Ishikawa cell line increased migratory ability and response to cisplatin. CBD reduced cell viability, activating predominantly apoptosis in type I cells and autophagy in mixed type EC cells. The CBD improved chemotherapeutic drugs cytotoxic effects, enhanced by TRPV2 over-expression. Hence, TRPV2 could be considered as a marker for optimizing the therapy and CBD might be a useful therapeutic option as adjuvant therapy.”

https://pubmed.ncbi.nlm.nih.gov/32751388/

https://www.mdpi.com/1422-0067/21/15/5409

Cytotoxic Effects of Cannabinoids on Human HT-29 Colorectal Adenocarcinoma Cells: Different Mechanisms of THC, CBD, and CB83

ijms-logo “In this study, we investigated the effects of exposition to IC50 dose for 24 h of a new synthetic cannabinoid (CB83) and of phytocannabinoids Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) on HT-29 colorectal carcinoma cells. Cell viability and proliferative activity evaluated using the MTT, lactate dehydrogenase (LDH), and CyQUANT assays showed that cell viability was significantly affected when CB83, THC, and CBD were administered to cells.

The results obtained showed that the reduced glutathione/oxidized glutathione ratio was significantly reduced in the cells exposed to CBD and significantly increased in the cells treated with the CB83 when compared to the controls. CBD treatment causes a significant increase in malondialdehyde content. The catalase activity was significantly reduced in HT-29 cells after incubation with CB83, THC, and CBD. The activities of glutathione reductase and glutathione peroxidase were significantly increased in cells exposed to THC and significantly decreased in those treated with CBD. The ascorbic acid content was significantly reduced in cells exposed to CB83, THC, and CBD. The ultrastructural investigation by TEM highlighted a significantly increased percentage of cells apoptotic and necrotic after CB83 exposition. The Annexin V-Propidium Iodide assay showed a significantly increased percentage of cells apoptotic after CB83 exposition and necrotic cells after CBD and THC exposition.

Our results proved that only CBD induced oxidative stress in HT-29 colorectal carcinoma cells via CB receptor-independent mechanisms and that CB83 caused a mainly CB2 receptor-mediated antiproliferative effect comparable to 5-Fuorouracil, which is still the mainstay drug in protocols for colorectal cancer.”

https://pubmed.ncbi.nlm.nih.gov/32752303/

https://www.mdpi.com/1422-0067/21/15/5533

Anti-Cancer Potential of Cannabinoids, Terpenes, and Flavonoids Present in Cannabis

cancers-logo“In recent years, and even more since its legalization in several jurisdictions, cannabis and the endocannabinoid system have received an increasing amount of interest related to their potential exploitation in clinical settings. Cannabinoids have been suggested and shown to be effective in the treatment of various conditions. In cancer, the endocannabinoid system is altered in numerous types of tumours and can relate to cancer prognosis and disease outcome. Additionally, cannabinoids display anticancer effects in several models by suppressing the proliferation, migration and/or invasion of cancer cells, as well as tumour angiogenesis. However, the therapeutic use of cannabinoids is currently limited to the treatment of symptoms and pain associated with chemotherapy, while their potential use as cytotoxic drugs in chemotherapy still requires validation in patients. Along with cannabinoids, cannabis contains several other compounds that have also been shown to exert anti-tumorigenic actions. The potential anti-cancer effects of cannabinoids, terpenes and flavonoids, present in cannabis, are explored in this literature review.”

https://pubmed.ncbi.nlm.nih.gov/32708138/

https://www.mdpi.com/2072-6694/12/7/1985

Enhancing ovarian cancer conventional chemotherapy through the combination with cannabidiol loaded microparticles

 European Journal of Pharmaceutics and Biopharmaceutics“In this work, we evaluated, for the first time, the antitumor effect of cannabidiol (CBD) as monotherapy and in combination with conventional chemotherapeutics in ovarian cancer and developed PLGA-microparticles as CBD carriers to optimize its anticancer activity.

Spherical microparticles, with a mean particle size around 25 µm and high entrapment efficiency were obtained. Microparticles elaborated with a CBD:polymer ratio of 10:100 were selected due to the most suitable release profile with a zero-order CBD release (14.13±0.17 μg/day/10 mg Mps) for 40 days.

The single administration of this formulation showed an in vitro extended antitumor activity for at least 10 days and an in ovo antitumor efficacy comparable to that of CBD in solution after daily topical administration (≈1.5-fold reduction in tumor growth vs control). The use of CBD in combination with paclitaxel (PTX) was really effective.

The best treatment schedule was the pre+co-administration of CBD (10µM) with PTX. Using this protocol, the single administration of microparticles was even more effective than the daily administration of CBD in solution, achieving a ≈10- and 8- fold reduction in PTX IC50 respectively. This protocol was also effective in ovo. While PTX conducted to a 1.5-fold tumor growth inhibition, its combination with both CBD in solution (daily administered) and 10-Mps (single administration) showed a 2-fold decrease.

These results show the promising potential of CBD-Mps administered in combination with PTX for ovarian cancer treatment, since it would allow to reduce the administered dose of this antineoplastic drug maintaining the same efficacy and, as a consequence, reducing PTX adverse effects.”

https://pubmed.ncbi.nlm.nih.gov/32682943/

https://www.sciencedirect.com/science/article/abs/pii/S0939641120302113?via%3Dihub

Anticancer Effect of New Cannabinoids Derived From Tetrahydrocannabinolic Acid on PANC-1 and AsPC-1 Human Pancreas Tumor Cells

View details for Journal of Pancreatic Cancer cover image

“New tetrahydrocannabinolic acid (THCA) derivatives ALAM027 and ALAM108 were proposed for the treatment of the pancreatic cancer disease.

Methods: The in vitro effect of new cannabinoids ALAM027 and ALAM108 was tested against PANC-1 and AsPC-1 cell lines by CellTiter Glo assay. Pancreatic cancer xenograft model was used for the in vivo anticancer activity study of these compounds on PANC-1 cells.

Results: The in vitro study of new cannabinoids showed greater activity of ALAM108 than ALAM027 both for PANC-1 and AsPC-1 cells. The in vivo study of new cannabinoids on PANC-1 cells showed that their oral administration was effective in reducing tumor volume and tumor weight, and did not lead to any discomfort and weight loss of mice.

Conclusion: The cannabinoids ALAM108 and ALAM027 inhibited the tumor growing 1.6-2 times in mice with human PANC-1 cells.”

https://pubmed.ncbi.nlm.nih.gov/32642629/

“The in vitro study of new cannabinoids showed greater activity of ALAM108 than of ALAM027 both for PANC-1 and AsPC-1 pancreas tumor cells. The in vivo study of these cannabinoids on PANC-1 cells showed that their oral administration decreased the tumor size 1.6–2 times and did not lead to any discomfort, psychotic effects, and weight loss of mice. Further study of these compounds will allow to determine the mechanism of their action on cancer cells and may open the way to new therapeutic drugs based on THCA.”

https://www.liebertpub.com/doi/10.1089/pancan.2020.0003

FIG. 1.

The Expression Level of Cannabinoid Receptors Type 1 and 2 in the Different Types of Astrocytomas

 SpringerLink“Astrocytomas, the most prevalent primary brain tumors, can be divided by histology and malignancy levels into four following types: pilocytic astrocytoma (grade I), diffuse fibrillary astrocytoma (grade II), anaplastic astrocytoma (grade III), and glioblastoma multiforme (grade IV). For high grade astrocytomas (grade III and grade IV), blood vessels formation is considered as the most important property.

The distribution of cannabinoid receptors type 1 (CB1) and cannabinoid receptor type 2 (CB2) in blood vessels and tumor tissue of astrocytoma is still controversial. Asrocytoma tissues were collected from 45 patients under the condition of tumor-related neurosurgical operation. The expression of CB1 and CB2 receptors was assessed using immunofluorescence, quantitative real-time RT-PCR and western blotting.

The results indicated an increased expression of CB1 receptors in tumor tissue. There was a significant difference in the mount of CB2 receptors in blood vessels. More was observed in the grade III and glioblastoma (grade IV) than astrocytoma of grade II and control.

This study suggested that, the expression increase of cannabinoid receptors is an index for astrocytoma malignancy and can be targeted as a therapeutic approach for the inhibition of astrocytoma growth among patients.”

https://pubmed.ncbi.nlm.nih.gov/32623617/

https://link.springer.com/article/10.1007%2Fs11033-020-05636-8

Cannabis, the Endocannabinoid System and Immunity-the Journey From the Bedside to the Bench and Back

ijms-logo“The Cannabis plant contains numerous components, including cannabinoids and other active molecules. The phyto-cannabinoid activity is mediated by the endocannabinoid system. Cannabinoids affect the nervous system and play significant roles in the regulation of the immune system.

While Cannabis is not yet registered as a drug, the potential of cannabinoid-based medicines for the treatment of various conditions has led many countries to authorize their clinical use. However, the data from basic and medical research dedicated to medical Cannabis is currently limited.

A variety of pathological conditions involve dysregulation of the immune system. For example, in cancer, immune surveillance and cancer immuno-editing result in immune tolerance. On the other hand, in autoimmune diseases increased immune activity causes tissue damage.

Immuno-modulating therapies can regulate the immune system and therefore the immune-regulatory properties of cannabinoids, suggest their use in the therapy of immune related disorders.

In this contemporary review, we discuss the roles of the endocannabinoid system in immunity and explore the emerging data about the effects of cannabinoids on the immune response in different pathologies. In addition, we discuss the complexities of using cannabinoid-based treatments in each of these conditions.”

https://pubmed.ncbi.nlm.nih.gov/32585801/

https://www.mdpi.com/1422-0067/21/12/4448