Seemingly diverse activities of beta-alethine.
beta-Alethine (beta-alanyl-cysteamine disulfide) exhibits striking biological activities in diverse systems. At an optimum of about 10 ng/ml, beta-alethine (a) adapts murine liver cells to culture (53 colonies/10(6) cells versus none in controls), (b) delays aging of human IMR-90 fetal lung fibroblasts (102 population doubling levels versus 47 in controls, producing 3 x 10(16) greater biomass), and (c) markedly stimulates antibody-producing plaque-forming cells from murine splenocytes (16,875/10(6) cells versus 55/10(6) cells in controls) or human peripheral blood leukocytes (1826/10(6) cells versus 0/10(6) cells in controls). Early interventions with beta-alethine (1 ng/kg to 100 micrograms/kg) successfully treat NS-1 myeloma in a syngeneic murine tumor model (NS-1 myeloma). Although there are indications in this model that beta-alethine is also effective when intervention is late, beta-alethine is ineffective in an allogeneic murine melanoma model (Cloudman S-91 melanoma). It is inferred that beta-alethine enhances cellular phenotypic expression, function, and vitality in diverse biological systems and may treat certain types of neoplasia. Because atomic spacings between the amide moieties in beta-alethine are the same as in the differentiating agent hexamethylene-bis-acetamide and because the radioprotectors WR 2721 and WR 1065 lack only the carbonyl oxygen of the thiol form (beta-aletheine), biological activities already reported for these compounds are compared with those presented herein for beta-alethine. Although these comparisons have not been made in the same systems, the tentative conclusion is that the amide moieties of beta-alethine may be critical to its potency and lack of obvious toxicity in cell culture and animal models.
Knight
G D
GD
School of Medicine, University of New Mexico, Albuquerque 87131.
Mann
P L
PL
Laubscher
K H
KH
Scallen
T J
TJ
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured / Q000187:drug effects; D016922:Cellular Senescence / Q000187:drug effects; D003543:Cysteamine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005347:Fibroblasts; D006801:Humans; D007962:Leukocytes / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009101:Multiple Myeloma / Q000188:drug therapy
D003543:Cysteamine; C090058:alethine