Repurposing Cannabidiol as a Potential Drug Candidate for Anti-Tumor Therapies
Abstract
:1. Introduction
2. Molecular Targets of Cannabidiol (CBD)
3. CBD and Cancer
Type/Cancer | Cell Line | Mechanism | Conclusion | Ref. |
---|---|---|---|---|
glioblastoma | U87/U373 in vitro/in vivo | ssDNA↑ | proliferation↓ apoptosis | [74] |
prostate ovarian | PC-3/DU145 OVCAR3 | GPR55/LPI↓ phospho ERK1/2↓ | proliferation↓ cell migration↓ | [93] |
glioblastoma | U87 | ROS↑ caspase↑ cytochrome c↑ CB1/CB2/TRPV1 receptor-independent TRPV2-activation Ca2+ influx↑ | apoptosis↑ migration↓ viability↓ (no effect at low doses) | [73,80,81] |
glioblastoma | U251/SF126 in vitro/in vivo | ERK↓ G0-G1 arrest ROS↑ Id-1↓ | cell survival↓ proliferation↓ apoptosis↑ aggressiveness↓ | [87,95] |
acute T lymphoblastic leukemia | Jurkat/MOLT-3/CCFR-CEM/K562/Reh/RS4 | mito Ca2+ overload mito transition pore formation↑ ROS↑ cytochrome c↑ | autophagy↑ apoptosis↑ | [75] |
breast | MDA-MB-231/MCF-7 | AKT/mTOR↓ BCL2↓ ROS↑ beclin1↑ direct/indirect activation CB2 and/or TRPV1 intracellular Ca2+↑ AKT/mTOR↓ cell cycle arrest GPR55↓ LPI↓ | apoptosis/ autophagy↑ migration↓ | [85,94] |
breast | SUM159/4T1/SCP2/MVT-1/MDA-MB-231/RAW 264.7 | GM-CSF/CCL3↓ NF-κB↓ EGFR/AKT↓ MAPK/ERK↓ | cell growth↓ metastasis↓ TME | [89] |
lung | A549/H460/H358 in vitro/in vivo | PAI-1↓ COX-2/PPAR-γ↑ ICAM-1↑ TIMP-1↑ MMP↓ | invasiveness↓ apoptosis↑ | [77,78,97] |
T lymphoblastoid leukemia | CEM/VLB(100) | P-gp↓ Rh123↑ | sensitivity↑ | [90] |
ovarian | 2008 | MRP1↓ Fluo3/vincristine↑ GPR55↓ LPI↓ | sensitivity↑ proliferation↓ | [91,93,104] |
immune cells | T/macrophages/NK cells | IFN-γ↓ IL-2↓ TNF-α↓ IL-10↑ GM-CSF↓ CCL3↓ NFAT↓ | proliferation↓ infiltration↓ | [89,105,106,107,108] |
primary endothelial cells | HUVEC | VEGF-2/VEGFA-2↓ MMP-2/9↓ uPA↓ ET-1↓ PDGF-AA↓ CXCL16↓ ERK/Akt↓ JNK↓ | angiogenesis↓ | [109,110] |
4. Tumor Microenvironment
5. Cannabinoids Inhibit Angiogenesis
6. Clinical Trials with CBD
7. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
References
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Receptor | Effect | Affinity | Sequence Identity |
---|---|---|---|
TRPV1 | agonist | ~78% [52] | 79% [52] |
TRPV2 | agonist | ~67% [52] | 96% [52] |
TRPV3 | agonist | ~54% [52] | 77% [52] |
TRPV4 | agonist | 15% [52] | 68% [52] |
TRPA1 | agonist | 108% [52] | ~30% [52] |
TRPM8 | antagonist | IC50 = 70–160 nM [53] | ~30% with TRPV2 [52] |
CB2 | inverse agonist | Ki = 4200 nM [53] | N |
CB1 | antagonist | Ki = 4900 nM [53] | N |
GPR55 | antagonist | IC50 = 445 nM [67] | N |
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Wang, F.; Multhoff, G. Repurposing Cannabidiol as a Potential Drug Candidate for Anti-Tumor Therapies. Biomolecules 2021, 11, 582. https://doi.org/10.3390/biom11040582
Wang F, Multhoff G. Repurposing Cannabidiol as a Potential Drug Candidate for Anti-Tumor Therapies. Biomolecules. 2021; 11(4):582. https://doi.org/10.3390/biom11040582
Chicago/Turabian StyleWang, Fei, and Gabriele Multhoff. 2021. "Repurposing Cannabidiol as a Potential Drug Candidate for Anti-Tumor Therapies" Biomolecules 11, no. 4: 582. https://doi.org/10.3390/biom11040582