Abstract
Background and aim: Breast cancer bone metastasis (BCBM) has a high incidence in clinical settings, resulting in decreased life expectancy and quality of life. Previous research has shown that Spatholobus suberectus Dunn inhibits breast cancer lung metastasis. However, no studies have examined its regulatory effects on BCBM. Hence, the present study aimed to investigate the inhibitory effect of the percolation of Spatholobus suberectus (SSP) on BCBM and its underlying mechanisms.
Experimental procedure: The inhibitory role of SSP on BCBM was determined by cytotoxicity, colony formation assays, invasion, and migration in triple-negative breast cancer (TNBC) cells, and osteoclast differentiation in RANKL-induced RAW 264.7 cell lines. The progression of bone metastasis and overall survival of mice were determined using the BCBM mouse model.
Results and conclusion: SSP treatment significantly reduced TNBC proliferation, migration, invasion, and colony formation and inhibited osteoclast differentiation. Additionally, SSP significantly decreased the expression of bone-related marker genes, such as tartrate-resistant acid phosphatase, cathepsin K, and osteoclast-associated receptors. SSP administration effectively reduced the progression of bone metastasis and prolonged the survival time of mice compared to that of the control. The expression level of Dickkopf-1 was also downregulated after SSP treatment, which may account for SSP's anti-bone metastasis mechanism. Overall, SSP exerts therapeutic effects by mitigating colony formation, invasion, migration, metastasis, osteoclast differentiation, and osteolytic destruction. This may provide new drugs for the prevention and treatment of BCBM.
Graphical abstract: The anti-breast cancer bone metastasis effect of SSP was mediated through different aspects: (1) direct tumor cell killing and cell motility inhibiting abilities; (2) repression of osteoclast differentiation induced by RANKL, which is rich in the bone resorption microenvironment; and (3) attenuation of osteoclast differentiation induced by MDA-MB-231 conditioned medium by reducing DKK1 secretion in vitro and tumor-induced osteolytic bone metastasis in vivo.
Experimental procedure: The inhibitory role of SSP on BCBM was determined by cytotoxicity, colony formation assays, invasion, and migration in triple-negative breast cancer (TNBC) cells, and osteoclast differentiation in RANKL-induced RAW 264.7 cell lines. The progression of bone metastasis and overall survival of mice were determined using the BCBM mouse model.
Results and conclusion: SSP treatment significantly reduced TNBC proliferation, migration, invasion, and colony formation and inhibited osteoclast differentiation. Additionally, SSP significantly decreased the expression of bone-related marker genes, such as tartrate-resistant acid phosphatase, cathepsin K, and osteoclast-associated receptors. SSP administration effectively reduced the progression of bone metastasis and prolonged the survival time of mice compared to that of the control. The expression level of Dickkopf-1 was also downregulated after SSP treatment, which may account for SSP's anti-bone metastasis mechanism. Overall, SSP exerts therapeutic effects by mitigating colony formation, invasion, migration, metastasis, osteoclast differentiation, and osteolytic destruction. This may provide new drugs for the prevention and treatment of BCBM.
Graphical abstract: The anti-breast cancer bone metastasis effect of SSP was mediated through different aspects: (1) direct tumor cell killing and cell motility inhibiting abilities; (2) repression of osteoclast differentiation induced by RANKL, which is rich in the bone resorption microenvironment; and (3) attenuation of osteoclast differentiation induced by MDA-MB-231 conditioned medium by reducing DKK1 secretion in vitro and tumor-induced osteolytic bone metastasis in vivo.
| Original language | English |
|---|---|
| Pages (from-to) | 1-9 |
| Number of pages | 9 |
| Journal | Journal of Traditional and Complementary Medicine |
| DOIs | |
| Publication status | E-pub ahead of print - 24 Nov 2024 |
User-Defined Keywords
- Spatholobus suberectus
- Breast cancer
- Bone metastasis
- Osteoclasts differentiation
- RAW264.7
