Xanthohumol kills B-chronic lymphocytic leukemia cells by an apoptotic mechanism.
B-chronic lymphocytic leukemia (B-CLL) is an indolent lymphoid malignancy with variable prognosis. Adverse prognostic factors comprise treatment resistance, cytogenetics (11q- and 17p-), the presence of unmutated Ig genes, and the more comprehensive activation marker Zap 70. In contrast to diminished sensitivity to chemotherapy, Zap 70+ B-CLL cells retain their responsiveness to manipulation of signal transduction and monoclonals. Xanthohumol (XA) has recently been documented to have an impact on breast cancer cell growth and invasiveness in vitro. Based on these observations, lymphocytes from patients with B-CLL were cultured in the presence of XA in vitro. XA induced a dose-dependent killing of B-CLL cells at an LD(50) ((24 h)) of 24.4 +/- 6.6 microM, independent of known adverse prognostic factors including functional loss of p53. Cell death was associated with poly (ADP)-ribose polymerase cleavage and annexin V positivity, suggestive of an apoptotic mechanism. Surprisingly, p 70(S 6 K) phosphorylation was stimulated upon XA treatment. In conclusion, XA has an antitumor activity on B-CLL cells in vitro. The molecular mechanisms behind this pro-apoptotic effect deserve further investigation.
Lust
Sofie
S
Department of Hematology, Ghent University Hospital, Gent, Belgium.
Vanhoecke
Barbara
B
Janssens
Ann
A
Philippe
Jan
J
Bracke
Marc
M
Offner
Fritz
F
D000368:Aged; D017209:Apoptosis / Q000187:drug effects*; D001402:B-Lymphocytes / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D005419:Flavonoids; D005434:Flow Cytometry; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011427:Propiophenones / Q000494:pharmacology*; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D014407:Tumor Cells, Cultured; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D005419:Flavonoids; D011427:Propiophenones; D011065:Poly(ADP-ribose) Polymerases; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C104536:xanthohumol