Table 1.
Anticancer studies of CBD.
| Cancer Type | Model | Dosage/ Treatment |
Effects | Reference |
|---|---|---|---|---|
| Lung Cancer | Non-small cell lung cancer (NSCLC) A549, H358, and H460 cell lines, and human-derived NSCLC cells | Up to 3 µM CBD | In NSCLC cell lines: ↓ Intercellular adhesion molecule-1 (ICAM-1)-dependent cell invasion; ↑ ICAM-1 and matrix metalloproteinases-1 (TIMP-1) via cannabinoid receptors, transient receptor potential vanilloid 1 (TRPV1), and p42/44 mitogen-activated protein kinase (MAPK) In primary NSCLC cells: ↓ ICAM-1-dependent cell invasion; ↑ ICAM-1 and TIMP-1 expression, CBD showed comparable anti-invasive efficacy to THC (3 µM) |
[26] |
| Athymic nude mice xenografted with A549 | 5 mg/kg CBD by intraperitoneal injection | ↓ Tumor size and number of metastatic nodules; ↑ ICAM-1 and TIMP-1 expression | ||
| A549, H460, and H358 | Up to 1 µM CBD | ↓ Cell invasion, plasminogen activator inhibitor-1 (PAI-1) via CB1, CB2, and TRPV1 receptors | [27] | |
| Athymic nude mice xenografted with A549 | 5 mg/kg CBD by intraperitoneal injection | ↓ Tumor size, PAI-1 protein expression | ||
| A549 | 10 µM CBD | ↓ Cell invasion; ↑ TIMP-1, p42/44, and p38 MAPKs via CB1, CB2, and TRPV1 receptors | [28] | |
| A549-xenografted nude mice | 5 mg/kg CBD by intraperitoneal injection | ↓ Number of metastatic nodules | ||
| A549 and H460, and primary cells from a lung cancer patient | 3 µM CBD | ↓ Cell viability; ↑ apoptosis, cyclooxygenase-2 (COX-2) and PPAR-γ, COX-2-dependent prostaglandins, PPAR-γ–dependent apoptotic cell death | [29] | |
| A549-xenografted nude mice | 5 mg/kg CBD by intraperitoneal injection | ↓ Tumor size and CD31 (vascularization marker); ↑ COX-2 and PPAR-γ | ||
| NSCLC A549 and H460 cell lines and human derived metastatic lung cancer cells | 3 µM CBD | ↑ Adherence to and lysis by lymphokine-activated killer (LAK) cells, ICAM-1 expression | [30] | |
| NSCLC cell lines A549, H460, H1792 | Tetrahydrocannabinol (THC) 30 µm, cannabidiol (CBD) 30 µm, and combination THC:CBD 10 µm each | All treatments: ↓ cancer cell proliferation, epithelial-to-mesenchymal transition (EMT), epidermal growth factor (EGF)-induced cell migration THC:CBD combination: ↓ epidermal growth factor receptor (EGFR) gene |
[31] | |
| A549 and H1299 NSCLC cell lines and H69 small cell lung cancer (SCLC) cell line | Up to 48 µM CBD; 10 µM CBD for treatment of stem cell spheres | ↓ Cell viability, stem cell sphere formation, expression of cancer stem cell genes (SOX2, POU5F1, CD44, or PROM1), mitochondrial membrane potential; ↑ cell death, caspase 3/7 protein, expression of apoptotic genes (TP53, CDKN1A, BAD, BCL2, BAX, or BAK1), levels of reactive oxygen species (ROS) | [32] | |
| Cisplatin-resistant (CR) NSCLC cell lines H460 and A549 | Up to 90 µM CBD | ↓ Cell viability, nuclear factor erythroid 2-related factor 2 (NRF-2) expression; ↑ apoptosis, ROS, sphere formation and protein expression of Snail, Nanog, and Vimentin | [33] | |
| NSG mice injected with H460-CR cells | 10 mg/kg CBD by intraperitoneal injection | ↓ Tumor progression and metastasis | ||
| Breast Cancer | MCF7 (estrogen receptor-positive) and MDA-MB-231 (triple-negative) | 20 µM CBD | ↓ Cell viability of both MCF7 and MDA-MB- 231; ↑ Endoplasmic reticulum stress, unfolded protein response (UPR) activation, intracellular ROS and Ca2+ accumulation via the activated TRPV1 receptor in the MCF7 | [34] |
| MCF7 | Up to 20 µM CBD | ↓ Bound NAD(P)H; ↑ mitochondrial concentrations of ROS and Ca2+ | [35] | |
| Estrogen receptor-positive (ER+) aromatase-overexpressing MCF-7aro | Up to 20 µM CBD | ↓ Cell viability, aromatase activity, ERα levels, cell cycle progression; ↑ autophagy, apoptosis, ERβ levels | [36] | |
| MCF7, MDA-MB-231, T47D, and SK-BR-3 | Up to 7 µM CBD | ↓ Cell viability, angiogenesis, stemness, hypoxia-induced factor-1α (HIF-1α) expression through Src/von Hippel–Lindau tumor suppressor protein (VHL) signaling, Slug and Vimentin (EMT-related proteins) | [37] | |
| MDA-MB-231 and MDA-MB-468 (triple-negative) | Up to 5 µM CBD in 2D cultures and up to 50 µM in 3D cultures | ↓ Cell viability (CBD had greater IC50 values in 3D than 2D), fibronectin, vimentin, and integrins-α5, -β5, and -β1, autophagy | [38] | |
| MDA-MB-468 | Up to 5 µM CBD in combination with doxorubicin (DOX) | ↑ DOX sensitivity in cancer cells, caspase 9; ↓ LOX and integrin-α5 | ||
| MDA-MB-231 cells and female nude mice injected with MDA-MB-468 cells | CBD-loaded extracellular vesicles (5 mg/kg) | ↑ DOX sensitivity in cancer cells and xenograft tumors, caspase 9, and BAX; ↓ interleukin-17 (IL-17), NF-κB, TGF-β, Bcl2 and mTOR | [39] | |
| MCF7 | 38.42–64.6 µM CBD in combination with DOX, docetaxel, paclitaxel, vinorelbine, and 7-ethyl-10-hydroxycamptothecin | Enhanced effects were observed with the combination of CBD and all chemotherapeutic drugs, while the strongest synergism was found between CBD and vinorelbine and 7-ethyl-10-hydroxycamptothecin; ↑ apoptosis | [40] | |
| Prostate Cancer | Androgen receptor (AR)-positive prostate cancer cell line LNCaP | Up to 15 µM CBD | ↓ Cell proliferation; ↑ phosphatases and phosphatase-dependent apoptosis, but cannabinoid receptor independent | [41] |
| AR-positive (LNCaP and 22RV1) and AR-negative (DU-145 and PC-3) cells | 1–10 µM CBD | ↓ Cell viability and AR (in LNCaP and 22RV1 cells); ↑ apoptosis, markers of intrinsic apoptotic pathways (p53-up-regulated modulator of apoptosis (PUMA), C/EBP homologous protein (CHOP) and intracellular Ca2+) partly due to TRPM8 antagonism, p53 (in LNCaP cells), and ROS | [23] | |
| PC-3 | 1 and 5 µM CBD | ↓ Exosome and microvesicle (EMV) release, CD63 exosomal marker, prohibitin, and STAT3 | [42] | |
| Colorectal Cancer (CRC) | SW480 | Up to 15 µM CBD | ↓ Cell proliferation; ↑ phosphatases and phosphatase-, CB1/CB2-dependent apoptosis | [41] |
| Caco-2 and HCT116 | 10 µM CBD | ↓ Cell proliferation via CB1, TRPV1, and PPARγ receptors, Akt activation, and DNA damage caused by an oxidative insult | [43] | |
| CRC induced by azoxymethane (AOM) in male ICR mice | 1 and 5 mg/kg CBD by intraperitoneal injection | 1 mg/kg: ↓ AOM-induced aberrant crypt foci (AFC), polyp and tumor formation, and Akt activation; ↑ apoptoic protein cleaved caspase-3 5 mg/kg: ↓ AOM-induced polyp formation |
||
| DLD-1 and HCT116 | Up to 5 µM CBD | ↓ Cell proliferation via CB1 receptor | [44] | |
| HCT116 | 1 and 2.5 µM CBD | ↓ Adhesion of HCT116 cells onto endothelial cells, invasiveness, migration via G protein-coupled receptor 55 (GPR55) | [45] | |
| HCT116 and DLD-1 | 6 µM CBD | ↓ Cell viability; ↑ apoptosis by regulating pro- and anti-apoptotic proteins (CHOP, inositol requiring enzyme-1α (RE1α), phosphorylated protein kinase RNA-like ER kinase (PERK), etc.), in a Noxa-and-ROS-dependent manner | [46] | |
| BALB/c nude mice injected with HCT116 Luc+ cells (a luminescent cell line derived from HCT116) | 10 and 20 mg/kg CBD by intraperitoneal injection | 20 mg/kg ↓ tumor size; ↑ apoptosis and Noxa expression | ||
| HCT116, HT29, and DLD-1 | 4 µM CBD | ↓ Cell viability; ↑ apoptosis by regulating pro- and anti-apoptotic proteins (CHOP, PERK, death receptor DR5 expression by ER stress, etc.), TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis | [47] | |
| Oxaliplatin-resistant DLD-1 and colo205 | 4 µM CBD | ↓ Cell proliferation, nitric oxide synthase 3 (NOS3), nitric oxide (NO), AMP-activated protein kinase (AMPK), TOR, and Akt; ↑ autophagic markers LC3 and p62, ROS via superoxide dismutase 2 (SOD2) causing mitochondrial dysfunction | [48] | |
| BALB/c mice injected with CT26 (mouse CRC cells) | 1 and 5 mg/kg CBD by intraperitoneal injection | ↓ Tumor size, cellular pleomorphism, vascular endothelial growth factor (VEGF), serum levels of IL-6 and IL-8 (5 mg/kg), and malondialdehyde (MDA); ↑ apoptosis, SOD (5 mg/kg), glutathione peroxidase (GPx) and glutathione reductase (GR) activity, and total antioxidant capacity | [49] | |
| HT-29 | 30 µM CBD | ↓ Cell viability, glutathione (GSH)-to-oxidized-glutathione (GSSG) ratio, ascorbic acid (AA), catalase (CAT), and GR and GPx activity; ↑ MDA and necrosis | [50] |