Cannabinoid Receptor Type 2 Agonist, GW405833, Reduced the Impacts of MDA-MB-231 Breast Cancer Cells on Bone Cells
Issued Date
2025-02-01
Resource Type
eISSN
20457634
Scopus ID
2-s2.0-85219114712
Journal Title
Cancer Medicine
Volume
14
Issue
4
Rights Holder(s)
SCOPUS
Bibliographic Citation
Cancer Medicine Vol.14 No.4 (2025)
Suggested Citation
Inson I., Chutoe C., Kanjanapipak J., Lertsuwan K. Cannabinoid Receptor Type 2 Agonist, GW405833, Reduced the Impacts of MDA-MB-231 Breast Cancer Cells on Bone Cells. Cancer Medicine Vol.14 No.4 (2025). doi:10.1002/cam4.70709 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/105585
Title
Cannabinoid Receptor Type 2 Agonist, GW405833, Reduced the Impacts of MDA-MB-231 Breast Cancer Cells on Bone Cells
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Abstract
Aim: Breast cancer frequently metastasizes to bones. The interaction between breast cancer cells and bone cells results in osteolytic lesions by disrupting the balance between osteoblast-mediated bone production and osteoclast-mediated bone resorption. This study aims to investigate the effects of the cannabinoid receptor type 2 (CB2) agonist, GW405833, on interactions between breast cancer cells and osteoblasts as well as its impact on breast cancer-induced osteoclastogenesis. Materials & Methods: MDA-MB-231, UMR-106, RAW 264.7 cells were used to represent breast cancer cells, osteoblast-like cells and macrophage-osteoclast precursor cells, respectively. Cell viability was evaluated by MTT assay, and breast cancer cell invasion was assessed by Transwell invasion assay. Tartrate-resistant acid phosphatase (TRAP) staining was utilized to evaluate osteoclastogenesis. Results: Our results demonstrated that GW405833 disrupted MDA-MB-231-induced UMR-106 cell death and promoted UMR-106 cell viability. The underlying mechanism of these effects was determined in this study. GW405833 reduced AKT phosphorylation in MDA-MB-231 cells without affecting mTOR protein expression or its phosphorylation. Conversely, in UMR-106 cells, GW405833 induced AKT and mTOR phosphorylated protein. Furthermore, the mTOR inhibitor reversed the GW405833-induced recovery of UMR-106 cell viability under MDA-MB-231-derived conditioned media (CM) exposure. These findings underscore the critical role of the AKT/mTOR pathway in mediating GW405833's inhibitory effects on cancer-bone interactions. Additionally, GW405833 suppressed osteoblast-enhanced breast cancer cell invasion and the expression of invasion-related proteins in both cell types, along with reducing osteoclastogenic factors induced by MDA-MB-231 CM in UMR-106 cells and suppressing MDA-MB-231 CM-enhanced osteoclastogenesis in RAW 264.7 cells. Conclusion: This study highlights the therapeutic potential of cannabinoid receptor agonist for treating breast cancer bone metastasis and bone-related complications.