Activation of cannabinoid receptors in breast cancer cells improves osteoblast viability in cancer-bone interaction model while reducing breast cancer cell survival and migration

Abstract

The endocannabinoid system has been postulated to help restrict cancer progression and maintain osteoblastic function during bone metastasis. Herein, the effects of cannabinoid receptor (CB) type 1 and 2 activation on breast cancer cell and osteoblast interaction were investigated by using ACEA and GW405833 as CB1 and CB2 agonists, respectively. Our results showed that breast cancer cell (MDA-MB-231)-derived conditioned media markedly decreased osteoblast-like UMR-106 cell viability. In contrast, media from MDA-MB-231 cells pre-treated with GW405833 improved UMR-106 cell viability. MDA-MB-231 cells were apparently more susceptible to both CB agonists than UMR-106 cells. Thereafter, we sought to answer the question as to how CB agonists reduced MDA-MB-231 cell virulence. Present data showed that co-activation of CB1 and CB2 exerted cytotoxic effects on MDA-MB-231 cells by increasing apoptotic cell death through suppression of the NF-κB signaling pathway in an ROS-independent mechanism. ACEA or GW405833 alone or in combination also inhibited MDA-MB-231 cell migration. Thus, it can be concluded that the endocannabinoid system is able to provide protection during breast cancer bone metastasis by interfering cancer and bone cell interaction as well as by the direct suppression of cancer cell growth and migration.

Use of Cannabis and Cannabinoids for Treatment of Cancer

“…Pharmacological activation or upregulation of CB1R and/or CB2R inhibits tumor growth and metastasis in vivo, attenuated proliferation, migration/invasion, and angiogenesis, and induced apoptosis in vitro through inhibition of extracellular signal-regulated kinase (ERK), protein kinase B (PKB)/AKT, cAMP/protein kinase A (PKA), c-Jun N-terminal kinase (JNK), MAPK p38, nuclear factor kappa B (NF-κB), and/or vascular endothelial growth factor (VEGF) signaling pathways, in various human cancers, including glioma [ 144 , 145 ], leukemia [ 146 , 147 , 148 ], multiple myeloma [ 149 ], neuroblastoma [ 150 ], breast [ 151 , 152 , 153 , 154 ], cervical [ 105 ], colorectal [ 110 , 155 , 156 , 157 ], endometrial [ 158 ], hepatocellular [ 159 ], intestinal [ 108 ], non-small-cell lung [ 160 , 161 ], prostate [ 162 , 163 ], and thyroid cancers [ 164 ]. The antitumorigenic and/or proapoptotic effects can be blocked by inhibition and/or knockdown of CB1R and/or CB2R [ 144 , 145 , 146 , 149 , 152 , 153 , 155 , 160 , 162 , 164 ].…”

Full spectrum cannabidiol oil reduces breast cancer cell viability and expression of epidermal growth factor receptor

“…Average percent cell viabilities are shown relative to control populations (Fig 1). TNBC cells have upregulated expression of the cannabinoid receptors CB1 and CB2 (Khunluck et al 2022). The susceptibility of TNBC cells to these agonists has only been recently appreciated.…”

Cannabis and cancer: unveiling the potential of a green ally in breast, colorectal, and prostate cancer

“…It also found that JWH-133 and WIN-55,212-2 decreased tumor volume and angiogenesis in a group of mice that were subcutaneously injected with BC cell line, MDA-MB-231 cells. It also found that both JWH-133 and WIN-55,212 reduced lung metastasis (Khunluck et al 2022 ).…”

“…This leads to cell cycle arrest and subsequent apoptosis (Zhong et al 2023 ). Study found that cannabinoid receptor agonists, JWH-133 and WIN-55,212-2, decreased cell viability and migration in BC cell lines, MDA-MB-231, and MDA-MB-468 cell lines (Khunluck et al 2022 ). It also found that JWH-133 and WIN-55,212-2 decreased tumor volume and angiogenesis in a group of mice that were subcutaneously injected with BC cell line, MDA-MB-231 cells.…”