There is an urgent need to develop innovative ways to treat breast cancer that has become resistant to established therapies. We seek to identify new agents by examining natural products with validated anticancer properties.

This study has focused on the cannabinoid CBD for cancer, which induces cytotoxicity in human glioma, leukemia, and breast cancer cells in vitro and inhibits metastasis of breast cancer cells. We explored the molecular mechanisms by which PCD-induced CBD in breast cancer cell lines, and examined the intricate relationship between CBD-induced apoptosis, autophagy, and ROS generation.

We found that CBD inhibited the survival of both estrogen receptor positive and estrogen receptor negative breast cancer cell lines and induced apoptosis in a concentration dependent manner. Furthermore, at these concentrations, CBD for cancer had little effect on MCF-10A cells, non-tumor mammary cells.

These data increase the convenience of CBD as an anticancer agent, because they suggest that CBD preferentially kills breast cancer cells, while minimizing damage to normal breast tissue.

Many cannabinoids mediate its effects by binding to CB1, CB2, or the vallinoid receptor. However, our results indicate that CBD induces PCD independent of these receptors.

This is a promising area for future research in that the identification of the receptor through which CBD for cancer, through its anticancer effects, may better inform the design of new drugs with a mechanism of action similar to CBD Oil.

In this study it was shown that CBD oil induced both apoptosis and autophagy-induced death in breast cancer cells. Apoptosis PCD is well documented, while autophagy mediated by cell death is a relatively recent discovery, and there is much to be learned about factors that prefer autophagy to self-protection or self-destruction.

CBD oil for cancer Recent studies support the growing evidence that ER stress can trigger autophagic cell death. Induction of ER stress was observed in MDAMB-231 cells within 2 hours of CBD treatment, followed by accumulation of LC3-II, leading us to conclude that CBD-induced autophagy in breast cancer cells it does not maintain homeostasis.

Rather, in this context, autophagy is cytodestructive and leads to PCD. Based on recent publications demonstrating that the AKT / mTOR pathway can inhibit autophagy, and that ER stress can block this pathway, the effect of CBD oil on AKT / mTOR signaling, which is dysregulated in many, was examined. neoplasms.

It was found that CBD decreased phosphorylation of AKT, mTOR, and 4EBP1, and decreased cyclin D1 levels in breast cancer cells. Furthermore, simultaneously with the inhibition of AKT / mTOR signaling, CBD raised the levels of PARP and LC3-II, markers for the induction of apoptosis and autophagy, respectively, suggesting that CBD oil may induce PCD in cells of breast cancer by inhibiting AKT / mTOR signaling.

Apoptosis may be induced by the intrinsic pathway (which is mediated by the mitochondria) or signaling of death receptors on the cell surface.

CBD was found to induce caspase-8 activation, t-BID generation and translocation to the mitochondria, cytochrome c SMAC release in the cytosol, and increased Fas-L levels.

These data support our hypothesis that CBD induces PCD through apoptosis-mediated mitochondria; However, CBD seems to initiate this form of PCD with both internal (t-BID translocation) and external stimuli (Fas-L, receptor death receptor).

We explored the relationship between CBD-induced apoptosis and autophagic cell death by blocking each form of PCD with specific caspase and autophagy inhibitors.

Inhibition of caspase decreased levels of CBD-induced apoptosis and protein markers in breast cancer cells, while inhibition of autophagy increased levels of CBD-induced apoptosis and protein marker expression.

These data suggest that blocking CBD oil-induced autophagy may affect a compensatory increase in apoptosis as an alternative means of PCD.

Beclin-1 can block autophagy when it forms a protein complex with Bcl-2. However, if beclin-1 is cleaved, this complex dissolution However, if beclin-1 is cleaved, this complex dissociates and autophagy is induced. Furthermore, this cleavage product translocates to the mitochondria and induces apoptosis by increasing cytocro release.