Xanthohumol Kills CLL Cells

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Sofie Lust, Barbara Vanhoecke, Ann Janssens, Jan Philippe, Marc

Bracke, and Fritz Offner

Xanthohumol kills B-chronic lymphocytic leukemia cells by an

apoptotic mechanism.

Mol Nutr Food Res, September 6, 2005; 49(9): 844-850.

Department of Hematology, Ghent University Hospital, Gent, Belgium.

Fax: +32-9-2402737.

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 Zap70. In contrast to diminished sensitivity to chemotherapy,

Zap70+ 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 muM, 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, p70(S6K) 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.

PMID: 16144030