Indirubin derivatives inhibit malignant lymphoid cell proliferation

Abstract

Indirubin-3′-monoxime (IO) is a derivative of indirubin, an active compound of a traditional Chinese medicinal recipe used to treat various inflammatory and malignant diseases. The main in vitro targets of IO (i.e. cyclin dependent kinases, glycogen synthase kinase-3β, Stat 3 and Aryl hydrocarbon receptor) are regulators of lymphocyte activation. We investigated the interest of IO and its derivative 6-bromo-indirubin-3′oxime (6BIO) for inhibiting the growth of malignant lymphoid cells. IO (1–20 μM) induced cell cycle inhibition and cell death in malignant B- (IM9, Reh6) and T- (Jurkat, CEM-T) lymphoid cell lines depending to cell type, doses, and duration of treatment. IO and 6BIO (10 μM) treatment for 24 and 48 h were compared: 6BIO treatment resulted in a stronger cytotoxicity and more profound inhibition of cell proliferation. Taken together, these results showed that IO and, moreover, its derivative 6BIO may be potent antiproliferative agents in malignant lymphoid cells.

Keywords:

• Indirubin
• lymphoid cells
• cell cycle
• apoptosis
• necrosis

Acknowledgements

This work was supported in part by the ‘Association pour la Recherche sur le Cancer’ (contract 5664) and by ‘La Ligue contre le Cancer, comité de Saône et Loire, de l'Ardèche et de la Drôme’.