Apoptosis Induction in Primary Human Colorectal Cancer Cell Lines and Retarded Tumor Growth in SCID Mice by Sulforaphane

We have investigated the anticancer effects of the dietary isothiocyanate sulforaphane (SFN) on colorectal cancer (CRC), using primary cancer cells lines isolated from five Taiwanese colorectal cancer patients as the model for colorectal cancer. SFN-treated cells accumulated in metaphase (SFN 6.25 μM) and subG1 (SFN 12.5 and 25 μM) as determined by flow cytometry. In addition, treated cells showed nuclear apoptotic morphology that coincided with an activation of caspase-3, and loss of mitochondrial membrane potential(ΔΨm). Incubations at higher SFN doses (12.5 and 25 μM) resulted in cleavage of procaspase-3 and elevated caspase-2, -3, -8, and -9 activity, suggesting that the induction of apoptosis and the sulforaphane-induced mitosis delay at the lower dose are independently regulated. Daily SFN s.c. injections (400 micromol/kg/d for 3 weeks) in severe combined immunodeficient mice with primary human CRC (CP1 to CP5) s.c. tumors resulted in a decrease of mean tumor weight by 70% compared with vehicle-treated controls. Our findings suggest that, in addition to the known effects on cancer prevention, sulforaphane may have antitumor activity in established colorectal cancer.

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Exploration of p53 plus interferon-beta gene transfer for the sensitization of human colorectal cancer cell lines to cell death

Cancer Biology & Therapy ◽

10.1080/15384047.2021.1899784 ◽

2021 ◽

pp. 1-10

Author(s):

Paulo Roberto Del Valle ◽

Samir Andrade Mendonça ◽

Fernanda Antunes ◽

Aline Hunger ◽

Rodrigo E Tamura ◽

...

Keyword(s):

Colorectal Cancer ◽

Cell Death ◽

Gene Transfer ◽

Cell Lines ◽

Cancer Cell ◽

Interferon Beta ◽

Human Colorectal Cancer ◽

Human Colorectal Cancer Cell ◽

Colorectal Cancer Cell Lines ◽

Beta Gene

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Action of a library of O-glycosylation inhibitors on the growth of human colorectal cancer cells in culture

Biochemical Society Transactions ◽

10.1042/bst0330721 ◽

2005 ◽

Vol 33 (4) ◽

pp. 721-723 ◽

Cited By ~ 11

Author(s):

G. Patsos ◽

V. Hebbe-Viton ◽

R. San Martin ◽

C. Paraskeva ◽

T. Gallagher ◽

...

Keyword(s):

Colorectal Cancer ◽

Cell Growth ◽

Cancer Cells ◽

Cell Lines ◽

Growth Patterns ◽

Limited Information ◽

Human Colorectal Cancer ◽

Human Colorectal Cancer Cell ◽

Colorectal Cancer Cells ◽

Colorectal Cancer Cell Lines

O-glycosylation is thought to play a significant role in the regulation of cell growth. However, only limited information is available, and few specific and selective inhibitors have been found. We have synthesized a library of O-glycosylation inhibitors based on benzyl-O-N-acetyl-D-galactosamine. These inhibitors were tested with an established series of human colorectal cancer cell lines, which model the adenoma-carcinoma sequence. Cancer cells were incubated with the inhibitors, and examined for cell growth patterns, and cellular and subcellular glycosylation using a range of lectins with confocal microscopy. The specificity of O-glycan inhibition was confirmed for the library, relative to other forms of glycosylation. All inhibitors tested resulted in smaller cell yields. However, a differential effect on O-glycosylation was detected using the lectins showing variation of localization at a subcellular level in the various cell lines. Further differential action of the inhibitor library was observed for apoptosis and on the cell cycle with the cell lines tested. This work demonstrates that O-glycosylation is closely involved in the regulation of cell growth in colorectal cancer cells and that the generation of a library of low-molecular-mass inhibitors offers a valuable means of examining this regulation at the molecular level.

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