Inhibition of MDA-MB-231 breast cancer cell migration and invasion activity by andrographolide via suppression of nuclear factor-κB-dependent matrix metalloproteinase-9 expression

Breast cancer is one of the most common types of cancer worldwide. The majority of patients with cancer succumb to the disease as a result of distant metastases (for example, in the bones), which cause severe complications. Despite advancements in breast cancer treatment, chemotherapeutic outcomes remain far from satisfactory, prompting a search for effective natural agents with few side-effects. Andrographolide (AP), a natural diterpenoid lactone isolated from Andrographis paniculata, inhibits cancer cell growth. The current study aimed to examine the effect of AP on breast cancer cell proliferation, survival and progression in vitro and also its inhibitory activity on breast cancer bone metastasis in vivo. To achieve this, CCK8, flow cytometry, migration, invasion, western blot, PCR and luciferase reporter assay analyses were performed in vitro as well as establishing intratibial xenograft model of breast cancer bone metastasis in vivo. The results demonstrated that AP inhibits the migration and invasion of the MBA-MD-231 aggressive breast cancer cell line at non-lethal concentrations, in addition to suppressing proliferation and inducing apoptosis at high concentrations in vitro. In vivo, AP significantly inhibited the growth of tumors planted in bone and attenuated cancer-induced osteolysis. Tartrate-resistant acid phosphatase staining revealed osteoclast activation in tumor-bearing mice and AP was observed to attenuate this activation. The anti-tumor activity of AP in vitro and in vivo correlates with the downregulation of the nuclear factor a signaling pathway and the inhibition of matrix metalloproteinase-9 expression levels. These results indicate that AP may be an effective anti-tumor agent for the treatment of breast cancer bone metastasis.