In a 2011 study, researchers examined the effects of cannabidiol (CBD) on breast cancer cells and discovered a complex relationship between autophagy, apoptosis, and CBD-induced programmed cell death. The study found that CBD preferentially induced cell death in breast cancer cells through the crosstalk of apoptosis and autophagy and suggested a potential mechanism for this effect by inducing endoplasmic reticulum stress, inhibiting AKT and mTOR signaling, and promoting reactive oxygen species generation.
The study used MDA-MB-231 cells, a highly aggressive human breast cancer cell line that is widely used in scientific research to study the molecular mechanisms of breast cancer. These cells are characterized by their high metastatic potential, invasiveness, and resistance to chemotherapy.
The study found that CBD induced concentration-dependent cell death in breast cancer cells, while having little effect on nontumorigenic cells. The cell death was found to occur through two distinct pathways, autophagy and apoptosis. Autophagy is a cellular process where damaged or unnecessary components of the cell are degraded and recycled, whereas apoptosis is a programmed cell death that occurs to maintain cellular homeostasis and eliminate damaged or abnormal cells.
The study also found that CBD interacts with specific proteins in the cell, such as beclin1, Vps34, and Bcl-2, which play crucial roles in the induction of apoptosis and autophagy. The study suggests that CBD does not mediate its effects through the direct binding of cannabinoid receptors or vallinoid receptors, but rather through other pathways. As of 2023, 12 years after this study was conducted, it is now well understood that CBD exerts its effects through multiple different pathways.
In the study, it was found that CBD triggers two pathways that lead to cell death in breast cancer cells. One pathway, known as the intrinsic pathway, is mediated by mitochondria, the powerhouse of the cell. The other pathway, known as the extrinsic pathway, is mediated by something called "death receptors." These death receptors are proteins that sit on the surface of cells and, when activated, can trigger a chain reaction that leads to cell death. In the case of CBD-induced extrinsic apoptosis, the study found increased levels of Fas-L, which is a protein that activates death receptors.
The study also observed the activation of caspase-8, a key protein involved in the extrinsic apoptosis pathway, as well as the translocation of t-BID to the mitochondria, which is a protein that connects the extrinsic and intrinsic pathways. The study suggests that CBD-induced cell death in breast cancer cells is the result of a complex interplay between these two pathways, as well as the balance between autophagy and apoptosis.
This finding also suggests that CBD may be able to overcome drug resistance mechanisms that often develop in cancer cells, as these mechanisms can impair both apoptosis and autophagy. Therefore, the ability of CBD to induce both apoptosis and autophagy highlights its potential as a novel and effective anticancer agent.
Overall, the study supports the potential of CBD as an alternative agent for breast cancer treatment. The study's findings on the complex relationship between autophagy, apoptosis, and CBD-induced programmed cell death provide valuable insights into the molecular mechanisms behind CBD's anticancer effects. This study highlights the potential of CBD as a promising alternative treatment for breast cancer, as it selectively induces cytotoxicity in breast cancer cells while minimizing damage to normal breast tissue.
Study Title: Cannabidiol induces programmed cell death in breast cancer cells by coordinating the cross-talk between apoptosis and autophagy
Study Link: https://pubmed.ncbi.nlm.nih.gov/21566064