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  • Adaptor Proteins, Antineoplastic Agents/pharmacology, Apoptosis/drug effects, Autophagy/drug effects, Breast Neoplasms/metabolism, Breast Neoplasms/pathology, Cannabidiol/pharmacology, Caspase Inhibitors, Cell Line, Dose-Response Relationship, Drug, Estrogen/metabolism, Female, Humans, Mitochondria/metabolism, Phosphoproteins/antagonists & inhibitors, Physiological/drug effects, Proto-Oncogene Proteins c-akt/antagonists & inhibitors, Reactive Oxygen Species/metabolism, Receptors, Signal, Signal Transduction/drug effects, stress, TOR Serine-Threonine Kinases/antagonists & inhibitors, Transducing/antagonists & inhibitors, Tumor
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Cannabidiol Induces Programmed Cell Death in Breast Cancer Cells by Coordinating the Cross-talk between Apoptosis and Autophagy

Cannabidiol (CBD), a major nonpsychoactive constituent of cannabis, is considered an antineoplastic agent on the basis of its in vitro and in vivo activity against tumor cells. However, the exact molecular mechanism through which CBD mediates this activity is yet to be elucidated. Here, we have shown CBD-induced cell death of breast cancer cells, independent of cannabinoid and vallinoid receptor activation. Electron microscopy revealed morphologies consistent with the coexistence of autophagy and apoptosis. Western blot analysis confirmed these findings. We showed that CBD induces endoplasmic reticulum stress and, subsequently, inhibits AKT and mTOR signaling as shown by decreased levels of phosphorylated mTOR and 4EBP1,...
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