Anticancer and chemosensitization effects of cannabidiol in 2D and 3D cultures of TNBC: involvement of GADD45α, integrin-α5, -β5, -β1, and autophagy

Mechanisms of Cannabidiol (CBD) in Cancer Treatment: A Review

“…Similar to the finding in NSCLC cells [ 31 ], a low dose of CBD (2 µM) was able to decrease the expression of the EMT-related proteins Slug and Vimentin in breast cancer cells [ 37 ]. In addition to regular 2D cell cultures, the efficacy and mechanism of CBD against breast cancer in 3D cultures was assessed by Surapaneni et al [ 38 ]. Interestingly, the IC 50 values of CBD in 3D cultures of triple-negative breast cancer MDA-MB-231 and MDA-MB-468 cells were much higher than in 2D cultures, reaching 20.18 and 33.85 µM, respectively (vs. 3.22 and 3.31 µM in the 2D cultures, respectively) [ 38 ].…”

“…In addition to regular 2D cell cultures, the efficacy and mechanism of CBD against breast cancer in 3D cultures was assessed by Surapaneni et al [ 38 ]. Interestingly, the IC 50 values of CBD in 3D cultures of triple-negative breast cancer MDA-MB-231 and MDA-MB-468 cells were much higher than in 2D cultures, reaching 20.18 and 33.85 µM, respectively (vs. 3.22 and 3.31 µM in the 2D cultures, respectively) [ 38 ]. 3D cell cultures generally mimic the in vivo settings of tumor microenvironments better than 2D cultures due to the complexity and heterogeneity of tumor microenvironments, such as cell–cell interactions, which could partially explain the higher IC 50 of CBD in 3D cultures [ 38 ].…”

“…Chemotherapy is one of the most frequently applied cancer treatments. In recent years, the potential synergistic effects of CBD and chemotherapeutic drugs against breast cancer have also been evaluated [ 38 , 39 , 40 ]. Doxorubicin (DOX) is a chemotherapy drug that is commonly used to treat many types of cancer, such as breast cancer, bladder cancer, and lymphoma.…”

“…However, it causes significant side effects, most notably cardiotoxicity, at high doses [ 63 ]. Two recent studies reported that when combined with CBD, DOX could be more effective than when administered alone [ 38 , 39 ]. When CBD (1–5 µM) was added to 0.5–1 µM of DOX, an increase in anti-proliferative and pro-apoptotic effects was observed.…”

“…When CBD (1–5 µM) was added to 0.5–1 µM of DOX, an increase in anti-proliferative and pro-apoptotic effects was observed. Furthermore, the protein expression of caspase-9, an initiating caspase of intrinsic apoptosis [ 64 ], was greatly increased with the combination treatment in MDA-MB-468 triple-negative breast cancer cells, and the effect was superior to either agent alone [ 38 ]. Their follow-up study fabricated extracellular vesicles encapsulated with CBD (CBD EVs) through sonication for sustained release and improved intracellular and intratumoral uptake [ 39 ].…”