Jasmonates Induce Apoptosis in CLL Cells, Not Normal Lymphocytes

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Abstract Number: 2534

Jasmonates induce death in leukemic cells from CLL patients but not in

normal peripheral blood lymphocytes

Orit Fingrut, Dorit Blickstein, Mati Shaklai, Eliezer Flescher, Tel

Aviv University, Tel Aviv, Israel; Rabin Medical Center Beilinson

Campus, Felsenstein Medical Research Center, Petach Tikva, Israel.

Jasmonates are a group of plant stress hormones. We have recently

shown jasmonates to be a novel class of anti-cancer agents in vitro

and in mice.

Three jasmonates: methyl jasmonate (MJ), jasmonic acid (JA) and

cis-jasmone (CJ), induced apoptosis in the human leukemic cell line

Molt-4, and MJ enhanced significantly the survival of lymphoma-bearing

mice. Furthermore, we found that jasmonates do not cause any harm to

normal lymphocytes taken from the peripheral blood of healthy donors.

The overall purpose of the present study was to evaluate the potential

clinical relevance of our former findings. Specifically, we

hypothesized that jasmonates are capable of exerting a cytotoxic

effect upon leukemic cells taken from the blood of human cancer

patients. We chose to test this hypothesis on cancer cells from

chronic lymphocytic leukemia (CLL) patients because these cells can be

easily distinguished (by multi-color FACS analysis) from normal

lymphocytes due to their abnormal co-expression of the CD5 and CD19

markers.

The three jasmonates induced cell death in CLL peripheral blood

lymphocytes (separated by Ficoll hypaque gradient centrifugation) in

the same order of efficiency as their cytotoxic effect towards Molt-4

cells: MJ>CJ>JA.

Nevertheless, samples taken from patients exhibited vastly different

levels of susceptibility to the jasmonate cytotoxic effect (e.g., the

effect of MJ on samples from different patients ranged 25-95%). These

differences could not be explained by medication, age or sex.

In order to further analyze this differential response, we determined

the percentage of (CD5+CD19+) cells in each blood sample. We found a

very significant positive correlation (R2=0.8519) between the

percentage of double-positive cells and the cytotoxic effect of MJ in

samples taken from CLL patients.

In conclusion, our results suggest that jasmonates are capable of

inducing cell death selectively in leukemic cells present in the blood

of CLL patients.

Presenter: Eliezer Flescher

Affiliation: Tel Aviv University, Tel Aviv, Israel. Email:

flascher@...

Copyright © 2003 American Association for Cancer Research. All rights

reserved. Published in the Proceedings of the AACR, Volume 44, March 2003.