Pandey R, Chander R, Sainis KB.Prodigiosins: a novel family
of immunosuppressants with anti-cancer activity.
Indian J Biochem Biophys. 2007 Oct;44(5):295-302.
Radiation Biology and Health Sciences Division, Bhabha Atomic
Research Centre, Trombay, Mumbai 400 085, India.
ruchipandey01@gmail.com
Prodigiosins (PrGs) are a family of promising therapeutic
molecules, isolated mostly from Gram-negative bacteria and
characterized by a common pyrryldipyrrylmethene structure with
varying side chains. They show a broad spectrum of activities
such as anti-microbial, anti-malarial, anti-cancer and
immunosuppressive. PrGs are attracting increasing attention due
to the ongoing research for less toxic, but effective agents for
cancer chemotherapy and immunosuppression for preventing
allograft rejection and autoimmunity. Different analogues have
been synthesized and evaluated. This review discusses the
immunosuppressive and anti-cancer activities of this class of
compounds, as both involve inhibition of cell proliferation. The
main focus is on the in vitro and in vivo immunosuppressive
activity of the different PrGs and the mechanisms involved. PrGs
primarily target the T cells, though some effects are observed
on other cell types also. Unlike the well-known
immunosuppressant cyclosporin A, PrGs do not inhibit the
secretion of IL-2 but inhibit the mitogenic signaling from IL-2,
suggesting a different mechanism of action. Janus tyrosine
kinase 3 (Jak3) that associates with IL-2R upon activation is
considered as the molecular target for PrGs. Its restricted
expression makes Jak3 as an attractive target for
immunosuppressive therapy. However, the available literature
suggests that some other pathways are also influenced by the
PrGs. These may be important for the anti-cancer activity, as
well as immunosuppressive action. Therefore, PrGs appear to be
potential candidates for pharmaceutical development as
immunosuppressants and also as anti-cancer agents.
PMID: 18341204 |
