Cannabidiol enhances cytotoxicity of anti-cancer drugs in human head and neck squamous cell carcinoma

Abstract

Cannabidiol (CBD) has anti-tumorigenic activity. However, the anti-cancer effect of CBD on head and neck squamous cell carcinoma (HNSCC) remains unclear. The cytotoxicity of CBD on HNSCC was analyzed using cell survival and colony-forming assays in vitro. RNA-seq was used for determining the mechanism underlying CBD-induced cell death. Xenograft mouse models were used to determine CBD’s effects in vivo. CBD treatment significantly reduced migration/invasion and viability of HNSCC cells in a dose- and time-dependent manner. HNSCC mouse xenograft models revealed anti-tumor effects of CBD. Furthermore, combinational treatment with CBD enhanced the efficacy of chemotherapy drugs. Apoptosis and autophagy processes were involved in CBD-induced cytotoxicity of HNSCCs. RNA-seq identified decreased expression of genes associated with DNA repair, cell division, and cell proliferation, which were involved in CBD-mediated cytotoxicity toward HNSCCs. We identified CBD as a new potential anti-cancer compound for single or combination therapy of HNSCC.

Regulatory Effect of Cannabidiol (CBD) on Decreased β-Catenin Expression in Alopecia Models by Testosterone and PMA Treatment in Dermal Papilla Cells

“…Our current data suggest that novel efficacy of CBD is considered to have a modulating mechanism on decreased expression of β-catenin by testosterone or PMA. Numerous cell culture and animal studies showed antitumor effects of cannabinoids in various cancer types [ 36 , 37 ]. CBD may enhance uptake or increase the potency of certain drugs used to treat cancer suggesting that CBD might have promising efficacy for treatment for many types of diseases including alopecia and cancers [ 38 ].…”

Cannabidiol in Neurological and Neoplastic Diseases: Latest Developments on the Molecular Mechanism of Action

“…Some neural system cancers are presented in Table 2 . CBD inhibits cancer cell growth and migration and affects the disruption of F-actin integrity [ 82 , 83 , 84 , 85 , 86 , 87 ]. Moreover, CBD inhibits migration and invasion of endothelial cells and angiogenesis.…”

“…CBD can promote CDKN1A (p21) expression in cells. Increased p21 protein expression evokes cell cycle arrest via cyclin D inhibition and the stimulation of GADD45A/B expression [ 83 ]. CBD can also induce endoplasmic reticulum (ER) stress [ 87 , 89 ], inhibiting AKT and mTOR signaling and subsequently decreasing the levels of phosphorylated mTOR and cyclin D1.…”

“…CBD also increases the generation of reactive oxygen species (ROS) [ 90 , 91 , 92 ]. Finally, during CBD-treatment, cancer cells can be destroyed by the induction of apoptosis and/or autophagy ( Figure 5 ) [ 83 , 84 , 89 , 93 ].…”

Tamoxifen Sensitizes Acute Lymphoblastic Leukemia Cells to Cannabidiol by Targeting Cyclophilin-D and Altering Mitochondrial Ca2+ Homeostasis

“…Recent evidence has demonstrated that CBD is a promising anticancer drug as it exhibits pronounced cytotoxicity against several cancer types, with a preference against T-ALL [14 -17]. In addition to its anticancer properties, CBD has demonstrated broader benefits for cancer therapy through pain relief and enhancement of the cytotoxicity of anticancer drugs such as cisplatin, 5-fluorouracil or paclitaxel, a reduction of migration and metastasis and a limitation of the adverse effects of chemotherapy as in the case of doxorubicin use [18][19][20]. The antileukemic activity of TAM has been revealed in pre-clinical trials, using leukemic cell lines and primary cells, derived from leukemic patients [21][22][23][24][25].…”