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T. GIRBÉS JUAN AN. R. ACAD. NAC. FARM.

nigrina b/ebulina l que han mostrado ser efectivos contra células cancerosas que
sobreexpresan el receptor de transferrina y una inmunotoxina antitumoral contra
el CD105 de ratón que identifica a la células CD105+ y las destruye de manera
selectiva tanto in vitro como in vivo. Ello convierte a la nigrina b en una herra-
mienta útil en la inmunotoxiterapia del cáncer.

Palabras clave: Nigrina b.—Toxicidad.—Inmunotoxinas.—Cáncer.

SUMMARY

Nigrin b: a ribosome-inactivating protein from elder. Pharmaceutical
utility in the construction of inmmunotoxins and conjugates
for cancer therapy

The present work on the non-toxic ribosome-inactivating protein nigrin b from
elder (Sambucus nigra L.) bark considers the more significant data concerning this
protein and highlights its pharmaceutical projection as component for the cons-
truction of immunotoxins and conjugates for cancer therapy. Elder contains a
collection of ribosome-inactivating proteins particularly nigrins that seem to be
responsible of elder toxicity. Nigrin b (bark) has fruit (nigrin f) and leaves (nigrin
l) isoforms which accumulated during the early stages of development. Nigrin b is
103-104 times less toxic than ricin, a highly toxic protein present in the seeds of
Ricinus communis L. and which is being used in the construction of immunotoxins
for cancer therapy. Nigrin b is internalised by a temperature-independent pathway
in constrast to ricin which takes a temperature and brefeldin A-dependent pa-
thway. Lethal doses of nigrin b led to the irreversible specific injury of the intes-
tinal crypts which in turn promotes the splitting of the intestinal epithelium and
further lethal intestinal bleeding. Sub-lethal doses of nigrin b promoted only rever-
sible damage of the intestinal crypts. The data on nigrin b amino acid sequence
indicated that some differences in key amino acids in de sugar binding subdo-
mains of the B chains of ricin and nigrin b account for the different toxicities of
these proteins. Such nigrin b feature is very useful for the construction of the
«magic bullets» or intelligent medicaments able to interact and destroy specific
targets. As examples of these «magic bullets» we constructed conjugates containing
either nigrin b or ebulin l and transferrin which display specific cytotoxicity
towards cancer cells, and an immunotoxin against mouse-CD105 which kills mouse-
CD105+ cells both in vitro and in vivo. This makes to nigrin b a useful tool for
cancer immunotoxitherapy.

Key words: Nigrin b.— Toxicity.— Immunotoxin.— Cancer.

INTRODUCCIÓN

El saúco (Sambucus nigra) es una planta medicinal de gran tra-
dición en la medicina occidental desde la más remota antigüedad.

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