Cellular accumulation of antineoplaston AS21 in human hepatoma cells.
|
| Abstract |
Antineoplaston AS2-1 is a mixture of sodium salts of phenylacetic acid (PAA) and phenylacetylglutamine (PAG) in the ratio 4:1. The uptake of both compounds has been examined in human hepatoma cell line, Hep G-2. The accumulation of PAA was characterized by temperature sensitivity, saturability and energy dependency. Organic anions (probenecid, p-aminonohippuric acid and stilbene) inhibited PAA uptake suggesting the involvement of organic anion system in PAA transport. PAG cellular uptake exhibited dependency on metabolic energy, since the accumulation was sensitive to lowered temperature as well as to replacement of sodium ions by choline in the incubation medium. In contrast, the process showed tolerance to lithium ions as a substitute to sodium ions. This finding, together with the strong inhibition of PAG accumulation by histidine and glutamine, indicates that system N, known to be specific for hepatic tissue and the glutamine-preferring amino acid transport system, mediates PAG uptake. We conclude that PAG, through competition with glutamine for the same membrane carrier, may reduce glutamine transport leading to intracellular glutamine depletion. The physiological consequence of this biochemical event could be critical to cancer cells and therefore might contribute to the mechanism of antineoplaston AS2-1 action.
|
|---|---|
| Authors | D Sołtysiak-Pawłuczuk, S R Burzyński |
| Journal | Cancer letters (Cancer Lett) Vol. 88 Issue 1 Pg. 107-12 (Jan 06 1995) ISSN: 0304-3835 [Print] Ireland |
| PMID | 7850766 (Publication Type: Journal Article) |
| Chemical References |
|
| Topics |
|
Join CureHunter, for free Research Interface BASIC access!
Realize the full power of the drug-disease research graph!