Phospholipid analogues were studied with regard to their cytostatic activity on different tumour cell lines and on murine bone marrow cells. Compounds compared for their activity were alkylglycero- and alkyl-phosphocholines with the corresponding serines and the alkylphosphocholines and -serines with the corresponding phosphono derivatives. Moreover, compounds containing cytidine 5'-diphosphate instead of the phospho (or phosphono-) choline or serine moiety were studied. rac-2-Chloro-2-deoxy-2-deoxy-1-0-hexadecyl-glycero-3-phosphocholine (cpd. Id), hexadecylphosphocholine (cpd. Ia) as well as hexadecylphosphonocholine (cpd. Ib) inhibited growth of tumour cells in suspension and monolayer culture and their colony and cluster formation in agar culture but not that of bone marrow cells. The exchange of choline for serine in these compounds results in the loss of this type of antitumour specificity. However, dodecylphospho-L-serine (cpd. IIc) is as specific as the choline derivatives Ia, b, d mentioned. Thus, for serine compounds the specificity for tumour cells might depend in a critical way on the length of the alkyl chain. The phosphono compounds Ib, IIb show almost the same activity as the corresponding compounds hexadecylphosphocholine (cpd. Ia) or hexadecylphosphoserine (cpd. IIa). The CDP-derivatives (IIIa, d, e, f) inhibited growth of tumour cells in suspension or monolayer cultures but not the colony and cluster formation in agar (i.e. they do not decrease the plating efficiency) from either tumour or bone marrow cells.

Alkylation↗

PubMedDate not supplied

Effect of ALP analogs on inositol trisphosphate formation in H184 mammary epithelial cells before and after transfection with v-erb B oncogene.

The influence of cytostatically active alkyllysophospholipid analogs with different chemical structure on IP3 (inositol-1,4,5-trisphosphate) formation and intracellular Ca++ concentration was studied in human mammary epithelial cells before and after transfection with v-erb B oncogene DNA. Transformed cells showed an increased IP3 formation compared with normal cells. In the presence of ALP (alkyllysophospholipid) analogs IP3 formation is inhibited more strongly in transformed cells than in normal cells, dependent on the structure of ALP analogs. Furthermore, these compounds increased [Ca++]i (intracellular Ca++ concentration) in transformed cells much more strongly than in normal cells. From these results, obtained in pursuit of an oncogene-related cancer treatment, it follows that ALP analogs may inhibit processes in signal transduction in cells more strongly after transfection with a defined oncogene than before.

Alpharetrovirus↗

PubMedDate not supplied

Multiple effects of antitumor alkyl-lysophospholipid analogs on the cytosolic free Ca2+ concentration in a normal and a breast cancer cell line.

Synthetic alkyl-lysophospholipids (ALP) are a new class of antitumor agents which interact with the cell membrane and the intracellular signal transduction at several sites. We studied the modulation of the intracellular calcium concentration ([Ca++]i) induced by two alkylglycerophosphocholines as well as hexadecylphosphocholine and hexadecylphosphoserine in a nontumorigenic and in a tumorigenic breast cell line. We found three distinct [Ca++]i-modulating effects: a transient increase, a decrease and a sustained increase. Their relative contribution to the observed response varies with different cell types, with the proliferation state, with the structure and with the concentration of the ALP analogs. The transient as well as the sustained increase in [Ca++]i depend mainly on extracellular Ca++; however, the Ca++ influx-inducing pathways might be different. The multiple [Ca++]i-increasing and decreasing effects induced by ALP analogs are discussed in relation to their influence on numerous Ca(++)-dependent effects, e.g. proliferation, differentiation, apoptosis and cytotoxicity.

Alkylation↗