Cyclopamine and quercetin suppress the growth of leukemia and lymphoma cells.
BACKGROUND
Hedgehog (Hh) and Wnt signaling pathways are involved in the stimulation of growth of leukemia and lymphoma cells. In the present study, whether or not the Hh inhibitor, cyclopamine, and the Wnt inhibitor, quercetin, suppress cell growth was investigated.


METHODS
The effects of cyclopamine and quercetin on the in vitro growth and protein expression of ten acute leukemia and B-cell lymphoma cell lines were examined.


RESULTS
Cyclopamine and quercetin suppressed cell growth and induced apoptosis in seven and eight cell lines respectively. Cyclopamine decreased the level of Gli1 protein, a target gene product of Hh signaling. Quercetin decreased the level of Notch1 protein and its active fragment in the DND-41 T-lymphoblastic leukemia cell line with constitutive Notch activation.


CONCLUSIONS
Cyclopamine and quercetin suppress the growth of a number of leukemia and lymphoma cells. This finding suggests the potential use of these compounds in molecularly-targeted therapy for leukemia and lymphoma.
Kawahara
Tatsuo
T
Department of Laboratory Medicine, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8519, Japan.
Kawaguchi-Ihara
Noriko
N
Okuhashi
Yuki
Y
Itoh
Mai
M
Nara
Nobuo
N
Tohda
Shuji
S
D017209:Apoptosis / Q000187:drug effects; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D018922:HL-60 Cells; D006801:Humans; D019169:Jurkat Cells; D007938:Leukemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008223:Lymphoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D014176:Protein Biosynthesis / Q000187:drug effects; D011794:Quercetin / Q000494:pharmacology*; D051881:Receptor, Notch1 / Q000096:biosynthesis; D014157:Transcription Factors / Q000096:biosynthesis; D014704:Veratrum Alkaloids / Q000494:pharmacology*; D000071676:Zinc Finger Protein GLI1
C400551:GLI1 protein, human; C497761:NOTCH1 protein, human; D051881:Receptor, Notch1; D014157:Transcription Factors; D014704:Veratrum Alkaloids; D000071676:Zinc Finger Protein GLI1; D011794:Quercetin; C000541:cyclopamine