Category Archives: Cancer

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Cannabidiol: an alternative therapeutic agent for oral mucositis?

Category : Cancer

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Cannabidiol: an alternative therapeutic agent for oral mucositis?

J Clin Pharm Ther. 2017 Feb 12;:

Authors: Cuba LF, Salum FG, Cherubini K, Figueiredo MA

Abstract
WHAT IS KNOWN AND OBJECTIVE: Chemo- and radiotherapy are therapeutic modalities often used in patients with malignant neoplasms. They kill tumour cells but act on healthy tissues as well, resulting in adverse effects. Oral mucositis is especially of concern, due to the morbidity that it causes. We reviewed the literature on the etiopathogenesis of oral mucositis and the activity of cannabidiol, to consider the possibility of its use for the prevention and treatment of oral mucositis.
METHODS: We searched the PubMed database and selected complete articles published in English that met the inclusion criteria for the period 1998-2016. The search terms ‘cannabinoids’, ‘cannabidiol’, ‘oxidative stress’, ‘antioxidants’ and ‘oral mucositis’ were used.
RESULTS AND DISCUSSION: The control of oxidative stress may prevent and alleviate oral mucositis. Studies have demonstrated that cannabidiol is safe to use and possesses antioxidant, anti-inflammatory and analgesic properties.
WHAT IS NEW AND CONCLUSIONS: The literature on the use of cannabidiol in dentistry is still scarce. Studies investigating the use of cannabidiol in oral mucositis and other oxidative stress-mediated side effects of chemotherapy and radiotherapy on the oral mucosa should be encouraged.

PMID: 28191662 [PubMed – as supplied by publisher]

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Phytochemistry of Cannabis sativa L.

Category : Cancer

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Phytochemistry of Cannabis sativa L.

Prog Chem Org Nat Prod. 2017;103:1-36

Authors: ElSohly MA, Radwan MM, Gul W, Chandra S, Galal A

Abstract
Cannabis (Cannabis sativa, or hemp) and its constituents-in particular the cannabinoids-have been the focus of extensive chemical and biological research for almost half a century since the discovery of the chemical structure of its major active constituent, Δ(9)-tetrahydrocannabinol (Δ(9)-THC). The plant’s behavioral and psychotropic effects are attributed to its content of this class of compounds, the cannabinoids, primarily Δ(9)-THC, which is produced mainly in the leaves and flower buds of the plant. Besides Δ(9)-THC, there are also non-psychoactive cannabinoids with several medicinal functions, such as cannabidiol (CBD), cannabichromene (CBC), and cannabigerol (CBG), along with other non-cannabinoid constituents belonging to diverse classes of natural products. Today, more than 560 constituents have been identified in cannabis. The recent discoveries of the medicinal properties of cannabis and the cannabinoids in addition to their potential applications in the treatment of a number of serious illnesses, such as glaucoma, depression, neuralgia, multiple sclerosis, Alzheimer’s, and alleviation of symptoms of HIV/AIDS and cancer, have given momentum to the quest for further understanding the chemistry, biology, and medicinal properties of this plant.This contribution presents an overview of the botany, cultivation aspects, and the phytochemistry of cannabis and its chemical constituents. Particular emphasis is placed on the newly-identified/isolated compounds. In addition, techniques for isolation of cannabis constituents and analytical methods used for qualitative and quantitative analysis of cannabis and its products are also reviewed.

PMID: 28120229 [PubMed – in process]

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Targeting calcium signaling in cancer therapy.

Category : Cancer

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Targeting calcium signaling in cancer therapy.

Acta Pharm Sin B. 2017 Jan;7(1):3-17

Authors: Cui C, Merritt R, Fu L, Pan Z

Abstract
The intracellular calcium ions (Ca(2+)) act as second messenger to regulate gene transcription, cell proliferation, migration and death. Accumulating evidences have demonstrated that intracellular Ca(2+) homeostasis is altered in cancer cells and the alteration is involved in tumor initiation, angiogenesis, progression and metastasis. Targeting derailed Ca(2+) signaling for cancer therapy has become an emerging research area. This review summarizes some important Ca(2+) channels, transporters and Ca(2+)-ATPases, which have been reported to be altered in human cancer patients. It discusses the current research effort toward evaluation of the blockers, inhibitors or regulators for Ca(2+) channels/transporters or Ca(2+)-ATPase pumps as anti-cancer drugs. This review is also aimed to stimulate interest in, and support for research into the understanding of cellular mechanisms underlying the regulation of Ca(2+) signaling in different cancer cells, and to search for novel therapies to cure these malignancies by targeting Ca(2+) channels or transporters.

PMID: 28119804 [PubMed]

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Quantitative analyses of synergistic responses between cannabidiol and DNA-damaging agents on the proliferation and viability of glioblastoma and neural progenitor cells in culture.

Category : Cancer

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Quantitative analyses of synergistic responses between cannabidiol and DNA-damaging agents on the proliferation and viability of glioblastoma and neural progenitor cells in culture.

J Pharmacol Exp Ther. 2016 Nov 7;:

Authors: Deng L, Ng L, Ozawa T, Stella N

Abstract
Evidence suggests that the non-psychotropic cannabis-derived compound, cannabidiol (CBD), has anti-neoplastic activity in multiple types of cancers, including glioblastoma multiforme (GBM). DNA-damaging agents remain the main standard of care treatment available for patients diagnosed with GBM. Here we studied the anti-proliferative and cell-killing activity of CBD alone and in combination with DNA-damaging agents (temozolomide, carmustine or cisplatin) in several human GBM cell lines and in mouse primary GBM cells in cultures. This activity was also studied in mouse neural progenitor cells (NPCs) in culture to assess for potential central nervous system (CNS) toxicity. We found that CBD induced a dose-dependent reduction of both proliferation and viability of all cells with similar potencies, suggesting no preferential activity for cancer cells. Hill plot analysis indicates an allosteric mechanism of action triggered by CBD in all cells. Co-treatment regiments combining CBD and DNA-damaging agents produced synergistic anti-proliferating and cell-killing responses over a limited range of concentrations in all human GBM cell lines and mouse GBM cells as well as in mouse NPCs. Remarkably, antagonistic responses occurred at low concentrations in select human GBM cell lines and in mouse GBM cells. Our study suggests limited synergistic activity when combining CBD and DNA-damaging agents in treating GBM cells, along with little-to-no therapeutic window when considering NPCs.

PMID: 27821713 [PubMed – as supplied by publisher]

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Cannabinoids synergize with carfilzomib, reducing multiple myeloma cells viability and migration.

Category : Cancer

Cannabinoids synergize with carfilzomib, reducing multiple myeloma cells viability and migration.

Oncotarget. 2016 Oct 18;:

Authors: Nabissi M, Morelli MB, Offidani M, Amantini C, Gentili S, Soriani A, Cardinali C, Leoni P, Santoni G

Abstract
Several studies showed a potential anti-tumor role for cannabinoids, by modulating cell signaling pathways involved in cancer cell proliferation, chemo-resistance and migration. Cannabidiol (CBD) was previously noted in multiple myeloma (MM), both alone and in synergy with the proteasome inhibitor bortezomib, to induce cell death. In other type of human cancers, the combination of CBD with Δ9-tetrahydrocannabinol (THC) was found to act synergistically with other chemotherapeutic drugs suggesting their use in combination therapy. In the current study, we evaluated the effects of THC alone and in combination with CBD in MM cell lines. We found that CBD and THC, mainly in combination, were able to reduce cell viability by inducing autophagic-dependent necrosis. Moreover, we showed that the CBD-THC combination was able to reduce MM cells migration by down-regulating expression of the chemokine receptor CXCR4 and of the CD147 plasma membrane glycoprotein. Furthermore, since the immuno-proteasome is considered a new target in MM and also since carfilzomib (CFZ) is a new promising immuno-proteasome inhibitor that creates irreversible adducts with the β5i subunit of immuno-proteasome, we evaluated the effect of CBD and THC in regulating the expression of the β5i subunit and their effect in combination with CFZ. Herein, we also found that the CBD and THC combination is able to reduce expression of the β5i subunit as well as to act in synergy with CFZ to increase MM cell death and inhibits cell migration. In summary, these results proved that this combination exerts strong anti-myeloma activities.

PMID: 27769052 [PubMed – as supplied by publisher]

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TRPV2 is a novel biomarker and therapeutic target in triple negative breast cancer.

Category : Cancer

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TRPV2 is a novel biomarker and therapeutic target in triple negative breast cancer.

Oncotarget. 2016 May 27;

Authors: Elbaz M, Ahirwar D, Xiaoli Z, Zhou X, Lustberg M, Nasser MW, Shilo K, Ganju RK

Abstract
Transient receptor potential vanilloid type-2 (TRPV2) is an ion channel that is triggered by agonists like cannabidiol (CBD). Triple negative breast cancer (TNBC) is an aggressive disease with limited therapeutic options. Chemotherapy is still the first line for the treatment of TNBC patients; however, TNBC usually gains rapid resistance and unresponsiveness to chemotherapeutic drugs. In this study, we found that TRPV2 protein is highly up-regulated in TNBC tissues compared to normal breast tissues. We also observed that TNBC and estrogen receptor alpha negative (ERα-) patients with higher TRPV2 expression have significantly higher recurrence free survival compared to patients with lower TRPV2 expression especially those who were treated with chemotherapy. In addition, we showed that TRPV2 overexpression or activation by CBD significantly increased doxorubicin (DOX) uptake and apoptosis in TNBC cells. The induction of DOX uptake was abrogated by TRPV2 blocking or downregulation. In vivo mouse model studies showed that the TNBC tumors derived from CBD+DOX treated mice have significantly reduced weight and increased apoptosis compared to those treated with CBD or DOX alone. Overall, our studies for the first time revealed that TRPV2 might be a good prognostic marker for TNBC and ERα- breast cancer patient especially for those who are treated with chemotherapy. In addition, TRPV2 activation could be a novel therapeutic strategy to enhance the uptake and efficacy of chemotherapy in TNBC patients.

PMID: 27248470 [PubMed – as supplied by publisher]

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The Use of Medical Marijuana in Cancer.

Category : Cancer

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The Use of Medical Marijuana in Cancer.

Curr Oncol Rep. 2016 Jul;18(7):40

Authors: Birdsall SM, Birdsall TC, Tims LA

Abstract
The use of medical marijuana in cancer care presents a dilemma for both patients and physicians. The scientific evidence is evolving, yet much of the known information is still insufficient to adequately inform patients as to risks and benefits. In addition, evidence-based dosing and administration information on medical marijuana is lacking. Medical marijuana is now legal, on some level, in 24 states plus the District of Columbia, yet is not legal on the federal level. This review addresses the current state of the research, including potential indications, risks and adverse effects, preliminary data on anticancer effects, as well as legal and quality issues. A summary of the clinical trials underway on medical marijuana in the oncology setting is discussed.

PMID: 27215434 [PubMed – in process]

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Phyto-, endo- and synthetic cannabinoids: promising chemotherapeutic agents in the treatment of breast and prostate carcinomas.

Category : Cancer

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Phyto-, endo- and synthetic cannabinoids: promising chemotherapeutic agents in the treatment of breast and prostate carcinomas.

Expert Opin Investig Drugs. 2016 Sep 28;:1-13

Authors: Fraguas-Sánchez AI, Fernández-Carballido A, Torres-Suárez AI

Abstract
INTRODUCTION: The term ‘cannabinoids’ designates a family of compounds with activity upon cannabinoid receptors. Cannabinoids are classified in three groups: phytocannabinoids, endocannabinoids, and the synthetic analogues of both groups. They have become a promising tool in the treatment of cancer disease, not only as palliative agents, but also as antitumor drugs, due to their ability to inhibit the proliferation, adhesion, migration, invasion, and angiogenesis of tumour cells. Two of the cancers where they have shown high anticancer activity are breast and prostate tumours. Despite this potential clinical interest, several studies have also reported that cannabinoids can stimulate the proliferation of cancer cells at very low concentrations.
AREAS COVERED: The aim of this review is to evaluate the promising chemotherapeutic utility of phytocannabinoids, endocannabinoids, and synthetic cannabinoids in breast and prostate cancer.
EXPERT OPINION: Cannabinoids, in particular the non-psychoactive CBD, may be promising tools in combination therapy for breast and prostate cancer, due to their direct antitumor effects, their ability to improve the efficacy of conventional antitumor drugs and their usefulness as palliative treatment. Nevertheless, deeper studies to fully establish the mechanisms responsible for their antitumour and pro-tumour properties and their formulation in efficient delivery systems remain to be established.

PMID: 27633508 [PubMed – as supplied by publisher]

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Evaluation of Two Commercially Available Cannabidiol Formulations for Use in Electronic Cigarettes.

Category : Cancer

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Evaluation of Two Commercially Available Cannabidiol Formulations for Use in Electronic Cigarettes.

Front Pharmacol. 2016;7:279

Authors: Peace MR, Butler KE, Wolf CE, Poklis JL, Poklis A

Abstract
Since 24 states and the District of Columbia have legalized marijuana in some form, suppliers of legal marijuana have developed Cannabis sativa products for use in electronic cigarettes (e-cigarettes). Personal battery powered vaporizers, or e-cigarettes, were developed to deliver a nicotine vapor such that smokers could simulate smoking tobacco without the inherent pathology of inhaled tobacco smoke. The liquid formulations used in these devices are comprised of an active ingredient such as nicotine mixed with vegetable glycerin (VG) and/or propylene glycol (PG) and flavorings. A significant active ingredient of C. sativa, cannabidiol (CBD), has been purported to have anti-convulsant, anti-nociceptive, and anti-psychotic properties. These properties have potential medical therapies such as intervention of addictive behaviors, treatments for epilepsy, management of pain for cancer patients, and treatments for schizophrenia. However, CBD extracted from C. sativa remains a DEA Schedule I drug since it has not been approved by the FDA for medical purposes. Two commercially available e-cigarette liquid formulations reported to contain 3.3 mg/mL of CBD as the active ingredient were evaluated. These products are not regulated by the FDA in manufacturing or in labeling of the products and were found to contain 6.5 and 7.6 mg/mL of CBD in VG and PG with a variety of flavoring agents. Presently, while labeled as to content, the quality control of manufacturers and the relative safety of these products is uncertain.

PMID: 27621706 [PubMed]

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