“Extracts of phytocannabinoids from Cannabis sativa have been studied for therapeutic purposes. Although nonpsychoactive CBD has been studied as a promising anticancer drug because it induces apoptosis in many cancer cells, it is also known to induce several physiological changes.
In this study, we clarify the functional role it plays in the morphological characteristics of intracellular vesicle formation as well as apoptosis in A549 human lung cancer cells.
CBD treatment shows growth inhibition at concentrations above 20 μM, but FACS analysis shows low efficacy in terms of cell death. Microscopic observations suggest that multiple vesicles were detected in the cytoplasmic region of CBD-treated A549 cells.
CBD treatment upregulates apoptosis-related proteins, such as p53, PARP, RIP1, RIP3, Atg12, and Beclin, indicating that CBD regulates several types of cell death. CBD treatment also induced E-cadherin, PPARγ, clathrin, β-adaptin, and Tsg101, also known to be cellular-differentiation inducers or vesicle-formation components.
Treatment combining CBD with GW9662, a PPARγ inhibitor, reduced CBD-induced cytoplasmic vesicle formation. This indicates that PPARγ regulates the vesicle-formation mechanism. However, CBD-treated E-cad KO clones did not show this regulatory mechanism.
These results elucidate the pharmacological and molecular networks associated with CBD in PPARγ-dependent vesicle formation and the induction of apoptosis.”
https://pubmed.ncbi.nlm.nih.gov/35890134/
“Recently, the pharmacological efficacy of CBD has been focused on in many types of disease models. In this study, we have shown that CBD treatment upregulated cell death proteins, such as p53, PARP, RIP1, RIP3, Atg12, and Beclin. In addition, CBD treatment also induced E-cadherin, PPARγ, clathrin, β-adaptin, and Tsg101, also known to be cellular-differentiation inducers or vesicle-formation components.
We have also shown that PPARγ regulates the vesicle-formation mechanism. Therefore, not only have we confirmed cell death induction by CBD, we have also confirmed the regulation of vesicle formation by PPARγ in various cancer models.
Detailed molecuclar insights would enhance the therapeutic utilization of CBD without side effects. Cellular proliferation and death could be determined by a variety of molecular regulations in cellular networks composed of a variety of proteins. Moreover, the physiological changes in cells will be closely related to functional changes in intracellular organelles.
We suggest that an understanding of the complex intracellular network system is necessary to optimize the pharmacological efficacy of CBD. These steady research efforts will make significant progress in increasing the utilization of CBD, which has been restricted by legal regulations in some countries.”
https://www.mdpi.com/1424-8247/15/7/836/htm