By the time aggressive breast cancers begin to invade and metastasize surrounding tissue, survival and rehabilitation of the sufferer is highly unlikely. Very little is understood of the complex genetic processes at work during the final stages of the disease, and there are currently few treatment options available.
By the time aggressive breast cancers begin to invade and metastasize surrounding tissue, survival and rehabilitation of the sufferer is highly unlikely. Very little is understood of the complex genetic processes at work during the final stages of the disease, and there are currently few treatment options available. Cannabidiol could offer a viable means of combatting breast cancer.
The need for effective and safe therapeutic agents for breast cancer is urgent, as the prevalence rate is among the highest of all cancers; the emergence of cannabidiol (CBD) as a potential candidate is therefore greatly encouraging. Various studies have emerged in recent years attesting to the effectiveness of CBD in inhibiting the formation of tumors, or tumorigenesis, although there is still much research to undertake before the molecular mechanisms involved can be clearly defined. However, it has been demonstrated that the ability of CBD to regulate the Id-1 inhibitor protein, which is responsible for prevention of premature cell differentiation in healthy subjects, is highly significant.
The receptor-independent effect of Cannabidiol
It has been known for some years that the prevalence of CB1 and CB2 receptors in primary breast cancer tissue is abnormally high. However, the mechanism by which Cannabidiol is thought to prevent neoplasia (unrestricted proliferation of abnormal cells) is now proven to be independent of the actions of these receptors, despite their number.
In fact, Cannabidiol directly acts to reduce the expression of the Id-1 protein, which regulates the metastatic potential of breast cancers. This reduction effect is thus far entirely unique to CBD among known (non-toxic) exogenous agents. Prior to this discovery, the research into down-regulation of Id-1 involved an ‘antisense’ gene therapy approach that was impracticable on living beings. This therapy involves effectively ‘switching off’ the ID1 gene (which encodes the Id-1 protein) by creating tailored strands of nucleic acid which bind to the messenger RNA (termed the sense) of the gene. Even in vitro, results have thus far been insignificant. However, the CBD molecule appears to act as a natural ‘antisense’ – a revelation that has caused ripples of excitement within the field of oncological research.
Id (inhibitor of DNA-binding) proteins are crucial regulators of stem cell mitosis, and overexpression of these proteins at the primary tumor site has been shown to correspond with an increased proliferation rate of mutated cells. Id-1 particularly has been recognized for over a decade as active in breast cancer neoplasia: it interacts with cellular DNA to inhibit it from bonding with DNA-binding proteins, which have the ability to repair, replicate and modify DNA structure as required for normal cell differentiation. Overexpression of Id-1 is also thought to reduce healthy mammary epithelial cells’ ability to differentiate into various crucial daughter cells through the normal processes of cell repair and regeneration, and may also cause abnormal proliferation and invasion of surrounding tissue, even in non-cancerous cells.
Past studies consistently demonstrate the effect of Cannabidiol on breast cancer
In a 2006 study, various human breast cancer cells (including the most aggressive known cell line, MDA-MB231) were treated in vitro with five natural phytocannabinoid compounds – cannabidiol, cannabigerol, cannabichromene, cannabidiol acid and THC acid. Cannabidiol was shown to be the most effective inhibitor of neoplastic cell proliferation, and was effective even at very low molecular concentration. Further to this, human breast carcinoma cells were injected into mice to encourage in vivo growth of xenograft (cross-species transplanted) tumors; when administered via intraperitoneal injection, CBD proved most effective in inhibiting tumor growth. It was also shown to have a negligible effect on healthy cells with normal expression of Id-1. However, it is not just as an antineoplastic agent that CBD is so influential – as a cytotoxin, it directly attacks and destroys various types of cancer cell when administered in vitro, although these results may vary in vivo as the effect of CBD is modulated by receptors. Further research is necessary to ascertain the exact nature of the complex interplay between CBD and programmed cell death (PCD).
How Cannabidiol can actually kill breast cancer cells
A 2011 study further demonstrated that, through an interaction with the protein beclin-1, Cannabidiol was found to actually cause apoptosis (total self-destruction) of various cancer cell lines, rather than merely inhibiting mitosis. Beclin-1 is also known to play a key role in autophagy, or cellular self-degradation of non-vital components, which may lead to PCD. It has been demonstrated that CBD can induce both autophagy and apoptosis in human glioma (brain or spinal tumor) cells, as well as leukemia and other forms of cancer.
The discovery of this complex influence on these particular processes of cell death (which are the two types of PCD relevant to breast cancer) is highly significant. It was previously believed that the action of cannabinoids was dependent on the CB1 and CB2 receptors, as well as the vanilloid receptors (which respond to heat and acidity generated by organic compounds such as capsaicin, the active component in chili peppers). While the interaction between the vanilloid and endocannabinoid receptors and Cannabidiol does lead to a reduction in cell proliferation, CBD has comparatively low affinity for these receptors – although it is now thought that important interactions occur even at relatively low molecular concentrations. However, due to this perceived low affinity, research into CBD has largely focused on the apparently more significant effects stemming from receptor-independent action.
Cannabidiol influences apoptosis by interacting with key proteins found within the cancerous cell, causing the outer mitochondrial membrane to reduce in electrical potential, and disrupting the permeation to the cell interior of certain molecules that are vital to metabolism – basically ruining the cell wall and starving the cell. This leads to a drastic loss of cellular energy, activating the self-destruction process of apoptosis which occurs naturally in energy-starved cells. CBD clearly affects this process in breast cancer cells, while having a negligible effect on healthy surrounding tissue, making it a very viable candidate for deeper investigation. Although these findings have not yet been replicated in humans, the positive results thus far yielded provide ample justification for further research, and the possibility of a cure for one of humanity’s most devastating illnesses.