Effects of Platycodon grandiflorum on the Induction of Autophagy and Apoptosis in HCT-116 Human Colon Cancer Cells

Complex dietary sphingolipids such as sphingomyelin and glycosphingolipids have been reported to inhibit development of colon cancer. This protective role may be the result of turnover to bioactive metabolites including sphingoid bases (sphingosine and sphinganine) and ceramide, which inhibit proliferation and stimulate apoptosis. The purpose of the present study was to investigate the effects of sphingoid bases and ceramides on the growth, death, and cell cycle of HT-29 and HCT-116 human colon cancer cells. The importance of the 4,5-trans double bond present in both sphingosine and C2-ceramide (a short chain analog of ceramide) was evaluated by comparing the effects of these lipids with those of sphinganine and C2-dihydroceramide (a short chain analog of dihydroceramide), which lack this structural feature. Sphingosine, sphinganine, and C2-ceramide inhibited growth and caused death of colon cancer cells in time-and concentration-dependent manners, whereas C2-dihydroceramide had no effect. These findings suggest that the 4,5-trans double bond is necessary for the inhibitory effects of C2-ceramide, but not for sphingoid bases. Evaluation of cellular morphology via fluorescence microscopy and quantitation of fragmented low-molecular weight DNA using the diphenylamine assay demonstrated that sphingoid bases and C2-ceramide cause chromatin and nuclear condensation as well as fragmentation of DNA, suggesting these lipids kill colon cancer cells by Inducing apoptosis. Flow cytometric analyses confirmed that sphingoid bases and C2-ceramide increased the number of cells in the A0 peak indicative of apoptosis and demonstrated that sphingoid bases arrest the cell cycle at G2/M phase and cause accumulation in the S phase. These findings establish that sphingoid bases and ceramide induce apoptosis In colon cancer cells and implicate them as potential mediators of the protective role of more complex dietary sphingolipids in colon carcinogenesis.

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ID: 1029 Effects of carnosine on regulation of migration and invasion in human colorectal cancer cells

Biomedical Research and Therapy ◽

10.15419/bmrat.v4is.305 ◽

2017 ◽

Vol 4 (S) ◽

pp. 104 ◽

Cited By ~ 1

Author(s):

Po-Yu Lai ◽

Shu-Chen Hsieh ◽

Chih-Chung Wu ◽

Shu-Ling Hsieh

Keyword(s):

Colorectal Cancer ◽

Colon Cancer ◽

Cancer Cells ◽

Human Colon ◽

Migration And Invasion ◽

Colon Cancer Cells ◽

Human Colon Cancer ◽

Hct 116 ◽

Hct 116 Cells ◽

Human Colon Cancer Cells

Colorectal cancer is the third most commonly diagnosed cancer in the word. Carnosine is an endogenous dipeptide found in vertebrate skeletal muscles. It is known to have anti-fatigue, antioxidative, antihypertensive, antidiabetic, and cancer inhibiting effects. However, little research has been done regarding its influence on the metastasis of colon cancer. This study cultivated HCT-116 human colon cancer cells as a test model in order to investigate the impact of carnosine on the migration and invasion of human colon cancer cells. The results showed that 48-hour treatments of HCT-116 cells with 0.5, 1, or 5 mM carnosine each significantly inhibited the migration ability of the cells (P < 0.05). The 48-hour treatments with 0.5, 1, or 5 mM carnosine were also found to significantly reduce MMP-9 activity (P < 0.05), but not MMP-2 expression. Furthermore, when HCT-116 cells treated with 1 or 5 mM carnosine, invasion ability are significantly decreased and significantly increased E-cadherin expression (P < 0.05). On the other hand, the protein of TIMP-1, an inhibitor of MMP-9, is signification increased after 1 or 5 mM carnosine treatment (P<0.05). In addition, the u-PA protein level are significantly decreased after carnosine treatment. The results indicate that carnosine can regulate the migration and invasion by regulating MMPs and its regulator molecular expression in HCT-116 cells.

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