Enhanced cytocidal action of methotrexate by conjugation to concanavalin A

✍ Scribed by Takashi Tsuruo; Takao Yamori; Shigeru Tsukagoshi; Yoshio Sakurai

• Book ID: 102277498
• Publisher: John Wiley and Sons
• Year: 1980
• Tongue: French
• Weight: 442 KB
• Volume: 26
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.2910260518

✦ Synopsis

Abstract

A methotrexate/concanavalin‐A conjugate (MTX/Con‐A) was prepared by covalent cross‐linking. The extent of substitution was approximately 5 moles methotrexate (MTX) per mole concanavalin A (Con A). Inhibition of dihydrofolate reductase by the conjugate was only marginal when compared to MTX. However, MTX/Con‐A showed a 7‐ to 116‐times higher cytocidal activity than MTX against cultured KB cells and various established cell lines from mouse colon adenocar‐cinomas 26 and 38, and Lewis lung carcinoma. The effect of MTX/Con‐A was diminished when the conjugate was preincubated with α‐methyl‐D‐mannoside, a specific binding sugar to Con‐A. MTX/Con‐A efficiently incorporated into cells and retained in them for longer periods of time than was MTX. The strong cytocidal action of the conjugate could be explained by the higher incorporation rate and the longer retention time of the conjugate in the cells.