Skullcapflavone I inhibits proliferation of human colorectal cancer cells via down-regulation of miR-107 expression

Wen Zhang, W Li,  Xue Han

Abstract:

Colorectal cancer (CRC) is a common malignant tumor with high global increase and mortality. While Skullcapflavone I has been reported to exert anti-tumor effect in several cancers, its role in CRC has not previously been investigated. Recent studies have also demonstrated that microRNA-107 (miR-107) and tropomyosin alpha-1 (TPM1) are important regulators of cancer cell proliferation, but it remains unclear if these are involved in regulating the effect of Skullcapflavone I on CRC cells. This study therefore assessed the effects of Skullcapflavone I on CRC cell proliferation and investigated miR-107 and TPM1 regulatory effects on this process. The results showed that Skullcapflavone I significantly suppressed cell proliferation and viability and down-regulated PCNA and Cyclin D1protein levels. It also down-regulated miR-107 expression which then promoted TPM1 expression, but miR-107 over-expression abolished Skullcapflavone I anti-proliferative effects. Furthermore, Skullcapflavone I inhibited the activations of MEK/ERK and NF-κB signal pathway activation by regulating TPM1 in HCT116 cells. These results demonstrated that Skullcapflavone I increased the expression of TPM1 by down-regulating miR-107 and inhibiting the MEK/ERK and NF-κB signal pathways. It then inhibited HCT116 cell proliferation, and therefore Skullcapflavone I may provide new methodology in colorectal cancer treatment.