Anti-proliferative effect of honokiol on SW620 cells through upregulating BMP7 expression via the TGF-β1/p53 signaling pathway

Abstract

Honokiol (HNK), a natural pharmaceutically active component extracted from magnolia bark, has been used for clinical treatments and has anti-inflammatory, antiviral and antioxidative effects. In recent years, anticancer research has become a major hotspot. However, the underlying molecular mechanisms of how HNK inhibits colorectal cancer have remained elusive. The present study focused on elucidating the effects of HNK on the expression of bone morphogenetic protein (BMP)7 and its downstream interaction with transforming growth factor (TGF)-β1 and p53 in colon cancer. In in vitro assays, cell viability, cell cycle distribution and apoptosis were examined using Cell Counting Kit-8, flow cytometry and reverse transcription-quantitative PCR, respectively. In addition, the expression of BMP7, TGF-β1 and relevant signaling proteins was determined by western blot analysis. In vivo, the anticancer effect of HNK was assessed in xenografts in nude mice. Furthermore, immunohistochemistry was performed to evaluate the association between BMP7 and TGF-β1 expression in colon cancer. The results indicated that HNK inhibited the proliferation of colon cancer cell lines, with SW620 cells being more sensitive than other colon cancer cell lines. Furthermore, HNK markedly promoted the expression of BMP7 at the mRNA and protein level. Exogenous BMP7 potentiated the effect of HNK on SW620 cells, while knocking down BMP7 inhibited it. As a downstream mechanism, HNK increased the expression of TGF-β1 and p53, which was enhanced by exogenous BMP7 in SW620 cells. In addition, immunohistochemical analysis indicated a positive association between BMP7 and TGF-β1 expression. Hence, the present results suggested that HNK is a promising agent for the treatment of colon cancer and enhanced the expression TGF-β1 and p53 through stimulating BMP7 activity via the non-canonical TGF-β signaling pathway.