Indirubin derivatives inhibit malignant lymphoid cell proliferation.
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-3beta, 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 microM) 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 microM) 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.
Faculté Lyon-Sud, Université Lyon 1, Oullins, France.
Amel
A
Chebel
Sandrine
S
Kagialis-Girard
Regine
R
Catallo
Wei Wen
WW
Chien
Valérie
V
Mialou
Carine
C
Domenech
Cedric
C
Badiou
Isabelle
I
Tigaud
Martine
M
Ffrench
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D019927:Cyclin E / Q000378:metabolism; D051361:Cyclin-Dependent Kinase 6 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D019169:Jurkat Cells; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010091:Oximes / Q000494:pharmacology*; D013997:Time Factors
C483321:6-bromoindirubin-3'-oxime; D000903:Antibiotics, Antineoplastic; C493956:CDKN1A protein, human; C436291:CDKN1B protein, human; D018797:Cell Cycle Proteins; D019927:Cyclin E; D050759:Cyclin-Dependent Kinase Inhibitor p21; D007211:Indoles; D047908:Intracellular Signaling Peptides and Proteins; D010091:Oximes; C474021:indirubin-3'-monoxime; D050760:Cyclin-Dependent Kinase Inhibitor p27; D051361:Cyclin-Dependent Kinase 6