Differentiation‐promoting effect of 1‐O (2 methoxy) hexadecyl glycerol in human colon cancer cells

Abstract

Alkylglycerols are naturally occurring bioactive ether lipids found in great abundance in the livers of many marine species. In this study, we evaluated the differentiation-promoting potential of a methoxy substituted alkylglycerol--1-O (2 methoxy) hexadecyl glycerol (MHG)--to promote a more benign or differentiated phenotype in human colon cancer cells. Three cell lines with different biological and phenotypic properties were used. They were the moderately differentiated and growth factor-responsive Moser, the growth factor-unresponsive and malignant HT29, and the poorly differentiated and growth factor-unresponsive HCT116. Treatment of these cell lines with MHG resulted in a downmodulation of cellular proliferation, a reduced propensity for anchorage-independent growth, and a reduced capacity in cellular invasion. Induction of the colon-associated and differentiation-related molecule carcinoembryonic antigen was also observed in the three cell lines. Induction of the transformation-sensitive and differentiation-related glycoprotein fibronectin was observed in the HT29 cells. It is concluded that MHG was biologically active and promoted a more benign or differentiated phenotype in these colon cancer cells. Since differentiation-inducing agents may possess chemoprevention properties, the use of MHG and the alkylglycerols in inducing differentiation or in chemoprevention of malignant diseases warrants further investigation.

Resveratrol induces colon tumor cell apoptosis independently of p53 and precede by epithelial differentiation, mitochondrial proliferation and membrane potential collapse

“…16 HCT116 is a poorly differentiated and growth factor-insensitive cell type that is, however, responsive to various cellular stresses, including DNA damage and spindle disruption. 16,17 HCT116 cells and the p53-negative derivatives were grown in culture with an approximately equal doubling time (30 hr). Incubation with resveratrol at concentrations between 10 and 100 M resulted in the appearance, under the electron microscope and the light microscope after DAPI staining, of condensed nuclei and apoptotic bodies as early as 24 hr after treatment, regardless of p53 status (data not shown).…”

“…Scanning and transmission electron microscopy revealed that in HCT116 cells the ultrastructural features of differentiation are only weakly developed, in accord with previous findings indicating the poor differentiation of this cell type. 17 However, by 24 hr after resveratrol treatment and regardless of p53 status, cells had begun to assume a morphology resembling that of columnar absorptive cells, with an increase in size, a more polygonal shape, the development of a dense apical brush border and the arrangement of cells in tight contact with the appearance of desmosomes (Fig. 6a).…”

Platelet-activating factor activates mitogen-activated protein kinases, inhibits proliferation, induces differentiation and suppresses the malignant phenotype of human colon carcinoma cells

“…Ectopic expression of the PAF receptor in normal rat kidney mesenchymal fibroblasts, however, has been reported to suppress v-src-or v-ras-induced transformation (Kume and Shimizu, 1997). We had earlier shown that 1-O(2-methoxy) hexadecyl glycerol, a lipid with similar aliphatic fatty acid chains to that of PAF is biologically active and suppresses the malignant properties of human colon and prostate cancer cells (Wang et al, 1999;Reynolds et al, 2000). In this study, we showed that PAF-activated MAP kinases, induced a more differentiated phenotype and suppressed the malignant properties of human colon carcinoma cells.…”

“…(a) PAF and cellular proliferation. Cellular proliferation was determined by the MTT assay in 96-well culture plates as described previously (Wang et al, 1999). Briefly, cells were seeded into 96-well culture plates (200 ml per well at a density of 20 000 cells/ml) and allowed to attach overnight.…”

“…(Figure 1b). Since the induction of Waf1/p21 is associated with growth inhibition and the induction of differentiation (Di Cunto et al, 1998;Chakrabarty et al, 1998), we determined the effect of PAF on CEA production, a differentiationrelated marker for colon carcinomas (Chakrabarty et al, 1988;Guadagni et al, 1990;Reynolds et al, 1998Reynolds et al, , 2000Wang et al, 1999). A one-time treatment of these cells (healthy and actively proliferating) with PAF (5-10 mm) induced a significant increase in CEA production Figure 2 Effect of PAF on anchorage-independent growth and cellular invasion.…”