Apoptosis Induction by Wheat-flour Sphingoid Bases in DLD-1 Human Colon Cancer Cells

2002 ◽  
Vol 66 (10) ◽  
pp. 2228-2231 ◽  
Author(s):  
Tatsuya SUGAWARA ◽  
Mikio KINOSHITA ◽  
Masao OHNISHI ◽  
Teruo MIYAZAWA
2006 ◽  
Vol 70 (12) ◽  
pp. 2906-2912 ◽  
Author(s):  
Tatsuya SUGAWARA ◽  
Nobuhiro ZAIMA ◽  
Akiyo YAMAMOTO ◽  
Shota SAKAI ◽  
Ryoko NOGUCHI ◽  
...  

2002 ◽  
Vol 227 (5) ◽  
pp. 345-353 ◽  
Author(s):  
Eun Hyun Ahn ◽  
Joseph J. Schroeder

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.


2011 ◽  
Vol 2011 ◽  
pp. 1-13 ◽  
Author(s):  
Chi-Tai Yeh ◽  
Chih-Jung Yao ◽  
Jiann-Long Yan ◽  
Shuang-En Chuang ◽  
Liang-Ming Lee ◽  
...  

Aberrant activation of Wnt/β-catenin signaling plays an important role in the development of colon cancer. HS7 is an active fraction extracted fromTaiwanofungus camphoratus, which had been widely used as complementary medicine for Taiwan cancer patients in the past decades. In this study, we demonstrated the effects of HS7 on the growth inhibition, apoptosis induction, and Wnt/β-catenin signaling suppression in human colon cancer cells. HS7 significantly inhibited proliferation of HT29, HCT116, and SW480 colon cancer cells in a dose- and time-dependent manner. The apoptosis induction was evidenced by DNA fragmentation and subG1 accumulation, which was associated with increased Bax/Bcl-2 ratio, activation of caspase-3 and cleavage of PARP. By using Tcf-dependent luciferase activity assay, HS7 was found to inhibit theβ-catenin/Tcf transcriptional activities. In addition, HS7 strongly suppressed the binding of Tcf complexes to its DNA-binding site shown in electrophoretic mobility shift assay. This inhibition was further confirmed by the decreased protein levels of Tcf-4 andβ-catenin. Theβ-catenin/Tcf downstream target genes, such assurvivin,c-myc,cyclin D1,MMP7, andMT1-MMPinvolved in apoptosis, invasion, and angiogenesis were also diminished as well. These results indicate thatTaiwanofungus camphoratusmay provide a benefit as integrative medicine for the treatment of colon cancer.


2004 ◽  
Vol 53 (10) ◽  
pp. 503-510 ◽  
Author(s):  
Kazuhiko AIDA ◽  
Mikio KINOSHITA ◽  
Tatsuya SUGAWARA ◽  
Jisaburo ONO ◽  
Teruo MIYAZAWA ◽  
...  

2012 ◽  
Vol 75 (11) ◽  
pp. 1896-1902 ◽  
Author(s):  
Olga Wesołowska ◽  
Jerzy Wiśniewski ◽  
Kamila Środa-Pomianek ◽  
Aleksandra Bielawska-Pohl ◽  
Maria Paprocka ◽  
...  

2001 ◽  
Vol 120 (5) ◽  
pp. A493-A493
Author(s):  
J HARDWICK ◽  
G VANDENBRINK ◽  
S VANDEVENTER ◽  
M PEPPELENBOSCH

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