Phloroglucinol에 의한 HT-29 대장암 세포 증식 억제 효과

Abstract

Phloroglucinol, a polyphenol compound, derived from Ecklonia cava (known as brown algae) that has beneficial biological activities. In particular, phloroglucinol including anti-oxidant, anti-inflammatory, and anti-cancer activities. In the present study, we investigated the signaling pathways related to the anticancer effects of phloroglucinol in human colon cancer HT-29 cells. MTS assays revealed that phloroglucinol significantly induced cell death in a dose-dependent manner. Phloroglucinol treatment on HT-29 cell displayed apoptotic features, such as G0/G1 phase of the cell cycle arrest. Consistent with G0/G1 phase arrest, western blotting showed that decreased the expression of cdk4, cdk6, cyclinD1 and the increase of p27 expression was observed. We analyzed that phloroglucinol induced apoptosis leads to the formation of death-induced signaling complex of Fas, FADD, procaspase-8 and AIF. In addition to, these were accompanied by the mitochondrial membrane potential with activation of the bcl-2 family proteins. Also, This study is analyzed its effect on the insulin-like growth factor (IGF-IR) signaling pathways. Phloroglucinol inhibited the expression level of IGF-IR and IRS-I, PI3K, Akt. These results in the study also decreased the expression level of mammalian target of rapamycin (mTOR) in critical regulator of cellular growth and proliferation which was localized to downregulated p70S6K, RPS6, elF4B. Moreover, revealed the inhibition of IGF-IR associated protein expression level of Ras, Raf, MEK, mitogen-activated protein kinases (MAPKs) such as ERK phosphorylation. These results have important implications for understanding the roles of cell growth pathway in colon cancer cell tumorigenesis. Although further studies are required to the multiple mechanism, these findings suggest that phloroglucinol has effect to inhibit the proliferation of HT-29 human colon cancer cells. These were evaluated by measuring cell death via induction of apoptosis. Therefore, phloroglucinol has therapeutic potential in the pathogenesis of colon cancer in humans.