Abstract
INTRODUCTION: Recent evidence has demonstrated the anticancer potential of 3-acetyl-11-keto-β-boswellic acid (AKBA). The current study was performed to evaluate the anti-invasive and antimotility effect of AKBA against breast cancer (BC) cells. MATERIAL AND METHODS: The antiproliferative assay was used to evaluate cell viability. Wound healing assay and Transwell invasion assay were used for migration and invasion respectively. Annexin V FITC assay and microscopy were used to quantify and detect apoptosis. Zymography and immunoblotting analysis were used for gelatinase activity of matrix metalloproteinases (MMPs) and protein expression of signaling proteins involved in apoptosis, tumor cell invasion and motility of BC cells. RESULTS: AKBA exhibits significant inhibition of cell proliferation and suppresses BC cell motility. Mechanistically, AKBA suppresses migration and invasion, and attenuates MMP-2 and MMP-9 activity, which plays a key role in metastasis. Furthermore, a dose-dependent manner of AKBA promotes significant induction of apoptosis. Moreover, we observed that a higher concentration of AKBA reduces phosphorylation of EGFR, PI3K, and Akt with a subsequent decrease in MMP-9 and MMP-2 expression, and an increase in TIMP1 and E-cadherin expression. However, pre-treatment with EGF in BC cells restores significant cell motility and invasion even in the presence of AKBA, indicating that inhibition of cell migration by AKBA is operated by the EGFR/PI3K/Akt axis. Additionally, AKBA showed a significant inhibitory and strong synergistic effect on EGFR-mediated PI3K/Akt signaling associated proteins when compared with the known inhibitors gefitinib and erlotinib. CONCLUSIONS: AKBA exhibits potential antiproliferative effects by inducing apoptosis and suppresses tumor cell motility and invasion, which is mediated by the EGFR/PI3K/Akt axis in BC cells.