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

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.

KEYWORDS:

• Breast cancer
• cannabidiol
• cannabinoid receptors
• endocannabinoids
• endocannabinoid system
• phytocannabinoids
• prostate cancer
• Δ⁹‐tetrahydrocannabinol

Article highlights

• In recent decades, cannabinoids have become a promising tool in the treatment of cancer disease, not only as palliative agents, but also as antitumor drugs.

• Several medicines based on cannabinoids are approved in some countries to treat the cancer and chemotherapy side effects, such as nausea, vomiting, pain and lack of appetite.

• An abnormal expression of endocannabinoid system (cannabinoid receptors, endocannabinoids and the enzymes implicated in their synthesis and degradation) has been found in several tumour cells as compared to health tissues. It has been related to tumour aggressiveness and disease outcome, suggesting a role of cannabinoids in tumour progression.

• Cannabinoids have proved to reduce the proliferation, adhesion, migration, invasion and angiogenesis of numerous cancers. Breast and prostate cancer are two of the tumours where cannabinoids have shown a high anticancer activity. The molecular mechanisms responsible for these effects depend on the drug and tumour context, and are not fully established.

• Several studies have also reported that cannabinoids show biphasic effects, and at low concentrations are able to stimulate the tumour growth.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This paper was funded by the Universidad Complutense de Madrid and the Region of Madrid; A.I Torres-Suarez and A. Fernandez-Carballido are part of the research group ‘Parenteral administration of drugs’ (ref: 910939). A.I. Fraguas-Sánchez has received a University Staff Training fellowship (FPU) from the Ministerio de Educación, Cultura y Deporte (FPU14/06441).