Seemingly diverse activities of beta-alethine.

Abstract

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.

• Authors: G D Knight, P L Mann, K H Laubscher, T J Scallen
• Journal: Cancer research (Cancer Res) Vol. 54 Issue 21 Pg. 5636-42 (Nov 01 1994) ISSN: 0008-5472 [Print] United States
• PMID: 7923209 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Cysteamine
• alethine

Topics

• Animals
• Antibody Formation (drug effects)
• Cell Line
• Cells, Cultured (drug effects)
• Cellular Senescence (drug effects)
• Cysteamine (analogs & derivatives, pharmacology)
• Dose-Response Relationship, Drug
• Drug Screening Assays, Antitumor
• Female
• Fibroblasts
• Humans
• Leukocytes (immunology)
• Lymphocytes (immunology)
• Male
• Mice
• Mice, Inbred BALB C
• Multiple Myeloma (drug therapy)