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Published on: October 27, 2020
Cannabinoid Receptor Type 2 Agonist, GW405833, Reduced the Impacts of MDA-MB-231 Breast Cancer Cells on Bone Cells
Ingon Inson1, Chartinun Chutoe1, Janjira Kanjanapipak1
1Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok, Thailand.
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.
Insights
The cannabinoid receptor type 2 (CB2) agonist, GW405833, protects bone cells from breast cancer and reduces cancer cell invasion. This compound shows promise for treating breast cancer bone metastasis and related complications.
Area of Science:
- Oncology
- Pharmacology
- Cell Biology
Background:
- Breast cancer frequently metastasizes to bone, causing osteolytic lesions.
- These lesions result from disrupted bone remodeling, involving cancer cell interactions with bone cells.
- Understanding these interactions is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the effects of the CB2 agonist GW405833 on breast cancer cell-osteoblast interactions.
- To assess GW405833's impact on breast cancer-induced osteoclastogenesis.
- To elucidate the molecular mechanisms underlying GW405833's effects.
Main Methods:
- Utilized MDA-MB-231 (breast cancer), UMR-106 (osteoblast-like), and RAW 264.7 (macrophage-osteoclast precursor) cells.
- Assessed cell viability (MTT assay), invasion (Transwell assay), and osteoclastogenesis (TRAP staining).
- Investigated the role of the AKT/mTOR pathway in mediating GW405833's effects.
Main Results:
- GW405833 promoted osteoblast viability and reduced breast cancer cell-induced osteoblast death.
- GW405833 inhibited breast cancer cell invasion and expression of related proteins.
- GW405833 suppressed osteoclastogenesis and osteoclastogenic factors induced by breast cancer cells.
Conclusions:
- GW405833 demonstrates therapeutic potential for managing breast cancer bone metastasis.
- The compound effectively mitigates cancer-induced bone destruction and cancer cell invasion.
- Targeting CB2 receptors may offer a novel strategy for treating bone complications in breast cancer patients.
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