Influence of the Alkyllysophospholipid ET-18-OCH₃ on Methylnitrosourea-induced Rat Mammary Carcinomas

Abstract

This study describes the efficacy of the alkyllysophospholipid 1-octadecyl-2-methoxy-Sn-rac-glycero-3-phosphocholine (ET-18-OCH₃) in inhibiting the growth of methylnitrosourea-induced mammary carcinomas in Sprague-Dawley rats. In experiment A 2 x 10 mg/kg Et-18-OCH₃ were administered daily for 10 weeks prior to manifestation of mammary carcinomas which resulted in a significant inhibition of median tumor number and median tumor volume per rat. Treatment of established tumors (experiment B) with 6 and 60 mg/kg ET-18-OCH₃ daily for 3 weeks effected a stagnation in tumor growth for the higher dosage only with 90% tumor inhibition in comparison to untreated controls; at the same time, however, clear toxic effects were seen, thus indicating a narrow therapeutic index of ET-18-OCH₃ in single-drug therapy. Combination of ET-18-OCH₃ with compounds possessing a different toxicity spectrum is suggested.

Biological Activities, Mechanisms of Action and Biomedical Prospect of the Antitumor Ether Phospholipid ET-18-OCH3 (Edelfosine), A Proapoptotic Agent in Tumor Cells

“…in BD-VI rats [323]. Oral administration of 10 mg/kg ET-18-OCH 3 twice daily inhibited partially the growth of methylnitrosourea-induced mammary carcinomas in Sprague-Dawley rats [324]. This treatment was well tolerated without symptoms of toxicity.…”

New cytostatics—more activity and less toxicity

“…and alkylphosphocholines represent two related classes of anticancer agents that target the cell membrane (4,12,19). Selective sensitivity of chemically induced, autochthonous mammary carcinoma to these agents has been established recently (6,10,16). This sensitivity might be due to several reasons including the finding that MNU-and 7,12-dimethylbenzanthracene-induced rat mammary carcinomas are known BT AL to contain a mutated cH-ras oncogene resulting in the expression of an altered G-protein which is located in the membrane and involved in signal transduction (3).…”

Erufosine Induces Autophagy and Apoptosis in Oral Squamous Cell Carcinoma

“…As early as the late 1960s, Hansjörg Eibl replaced the glycerol-linked ester bond at position C1 of LysoPC by an ether linkage, and added another ether-linked methyl group at the C2 position. The resulting ether lipid, 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine (edelfosine, ET-18-OCH3; Figure 16.1; Berger et al, 1984), was found to be a potent immune modulator and an effective inhibitor of tumor cell proliferation. The antineoplastic properties of edelfosine have been evaluated in a broad panel of tumor and normal cells, as well as in mouse and rat tumor models, showing a high degree of selectivity towards tumor cells.…”