Antiproliferative activity of a pregnancy recognition hormone, ovine trophoblast protein-1.
Ovine trophoblast protein-1 (oTP-1) is the alpha-interferon (IFN alpha) variant, secreted by conceptuses and referred to as type I trophoblast interferon, that is responsible for maternal recognition of pregnancy in sheep. We have previously shown that oTP-1 is as potent an antiviral agent as any known IFN. IFNs also possess anticellular activity and are, in fact, used in cancer therapy and have been found to be effective in the treatment of cancer such as myelogenous and hairy cell leukemias. A significant problem with the currently used IFNs is the undesirable side effect of toxicity at high concentrations. In this study, we examined the anticellular activity and toxicity of oTP-1. It inhibited proliferation but did not exhibit toxicity at high concentrations, unlike known IFN alpha S. In an anticellular assay using colony formation of both the human amnionic line, WISH, and the bovine epithelial line, MDBK, oTP-1 inhibited both colony size and number. oTP-1 was as effective as human and bovine IFN alpha s on human and bovine cells, respectively; thus, it displays potent cross-species activity. Its activity was dose dependent, and inhibition of proliferation could be observed at concentrations as low as 1 unit/ml. Concentrations as high as 50,000 units/ml stopped proliferation, while viability was not impaired. Cell cycle analysis revealed an increased proportion of cells in S phase and a corresponding decreased proportion of cells in G2/M after 48 h of oTP-1 treatment. Therefore, oTP-1 appears to inhibit progress of cells through S phase. oTP-1 antiproliferative effects can be observed as early as 12 h after after the initiation of culture and are maintained through 6 days. Thus, oTP-1 exhibits potent anticellular activity without toxicity across species and may have therapeutic potential as an antitumor agent without the toxic effects generally associated with IFNs.
Pontzer
C H
CH
Department of Microbiology, University of Florida, Gainesville 32611.
Bazer
F W
FW
Johnson
H M
HM
D000818:Animals; D002417:Cattle; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D003114:Colony-Forming Units Assay; D003429:Cross Reactions; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007370:Interferon Type I; D016898:Interferon-alpha / Q000494:pharmacology; D008186:Luteolytic Agents / Q000037:antagonists & inhibitors; D011257:Pregnancy Proteins / Q000494:pharmacology*
D007370:Interferon Type I; D016898:Interferon-alpha; D008186:Luteolytic Agents; D011257:Pregnancy Proteins; C020947:interferon tau