Shark liver oil has been used for over 40 years as both a therapeutic and preventive agent. The active ingredients in shark liver oil have been found to be a group of ether-linked glycerols known as alkylglycerols. Initial clinical use was for treating leukemias, and later to prevent radiation sickness from cancer x-ray therapy. Studies over the last 30 years have shown that alkylglycerols are multifunctional. The level of natural alkylglycerols rises within tumor cells, apparently in an effort to control cell growth. Recent studies indicate that the activation of protein kinase C, an essential step in cell proliferation, can be inhibited by alkylglycerols. This action suggests a competitive inhibition of 1.2-diacylglycerol by alkylglycerols. Further studies on the immunostimulatory action of alkylglycerols suggest a primary action on the macrophage. The process of macrophage activation has been demonstrated with both synthetic and natural alkylglycerols. While the exact mechanism has not been found, both an autocrine and paracrine system have been suggested. Shark liver is a major natural source of alkylglycerols, which have no known side effects in dosages of 100 mg three times a day. The information presented in this article suggests that alkylglycerols may be used both as an adjunct therapy in the treatment of neoplastic disorders and as an immune booster in infectious diseases.

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.

The ability of the naturally occurring ether lipid, 1-O (2 methoxy) hexadecyl glycerol (MHG), and phenylbutyrate (BP) to inhibit cellular proliferation, anchorage-independent growth and cellular invasion in the human prostate cancer LnCap and DU145 cells was determined. Both MHG and PB inhibited the malignant properties of these prostate cancer cells. The concentrations required to achieve similar inhibitory effect, however, were significantly different for these two agents. MHG inhibited cell growth with equal potency in these cell lines with an IC-50 value of 93 microM for LnCap, and 97 microM for DU145. The IC-50 values for PB were 1.3 mM and 7.3 mM, respectively, for LnCap and DU145 cells. Both MHG and PB (IC-50 concentrations) inhibited the anchorage-independent growth and cellular invasion in these cells. Over 50% inhibition of anchorage-independent growth was achieved for both LnCap and DU145 cells by PB, while a lesser degree of inhibition was achieved with MHG. Both MHG- and PB-treated cells showed a reduced propensity to invade matrigels. Invasion of PB-treated LnCap and DU145 cells was reduced, respectively, by approximate 41 and 30% when compared to untreated control cells, while invasion of MHG-treated LnCap and DU145 cells was reduced to a lesser extent. Because differentiation-inducing agents may possess chemopreventive properties, the use of naturally occurring MHG and nontoxic PB in the chemoprevention of malignant diseases warrants further investigation.

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.