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Anticancer activities of adenine nucleotides in tumor bearing hosts
Author(s) -
Rapaport Eliezer
Publication year - 1993
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430280344
Subject(s) - extracellular , purine , adenine nucleotide , receptor , biology , adenosine triphosphate , cancer cell , nucleotide , metabolism , adenosine , biochemistry , pharmacology , chemistry , endocrinology , medicine , cancer , enzyme , gene
Abstract The utilization of adenosine 5′‐triphosphate (ATP) infusions against solid refractory cancers is based on the preclinical findings that low levels of extracellular ATP significantly inhibit the growth of a variety of human and murine tumor cells. The mechanisms of tumor cell killing by extracellular ATP are attributed to effects mediated by its interaction with P 2 purine receptors as well as non‐receptor‐mediated pore formation in the tumor cell membrane. The achievement of elevated extracellular blood plasma pools of ATP is accomplished by the administration of adenine nucleotides which yield elevated liver, red blood cell, and plasma compartment pools of ATP. Administration of AMP or ATP to tumor‐bearing murine hosts produced, in addition to the cytotoxic effects against the tumor, a variety of host mediated anticancer activities, including significant inhibition of host weight loss in cachectic tumor models. The inhibition of several adverse events Which are among the hallmarks of cancer cachexia is the result of prevention of the significant depletion of visceral energy stores in cachectic animals after the administration of adenine nucleotides, leading to the successful maintenance of hepatic functions, the resumption of normal protein synthesis in the liver, and inhibition of the synthesis of hepatic acute‐phase proteins. Thus, the administration of ATP as an anticancer agent in humans at levels (below 0.1 mg/kg min) which do not adversely affect systemic and cardiovascular functions is expected to lead to the following activities resulting from the generation of elevated hepatic, red blood cell, and blood plasma ATP pools: cytolytic effects against the tumor, inhibition of host weight loss, and other adverse effects of cachexia, anti‐pain effects, modulation of blood flow to the tumor, positive effects on motor functions and performance status due to increases in several other parameters which are also known to be affected by elevated red blood cell and blood plasma (extracellular) ATP levels. © 1993 Wiley‐Liss, Inc.