J. Appl. Biomed. 4: 135–139, 2006 ISSN 1214-0287 ORIGINAL ARTICLE Parthenolide has apoptotic and cytotoxic selective effect on B-chronic lymphocytic leukemia cells Gustavo Horacio Marin, Eduardo Mansilla Facultad de Ciencias Médicas, Universidad Nacional de La Plata, Argentina Received 12 th January 2006. Revised 14 th March 2006. Published online 10 th April 2006. Summary B-chronic lymphocytic leukemia (B-CLL) is the most common form of leukemia in the western world. It results from a relentless accumulation of small mature monoclonal lymphocytes. Following a recent demonstration of a significant increase in the proliferative pool of CLL cells in vivo, the gradual accumulation of malignant B-CLL cells seems to be primarily the consequence of their selective survival advantages relative to their normal B-cell counterparts. As the disease is mainly caused by defective apoptosis it is thus a good candidate for treatment by proapoptotic agents. Even though a large amount of research has been done during the last past years, the prognosis has not changed. Because of this, new therapeutic strategies are urgently needed, especially those that could switch on new apoptotic responses. In order to test the ability of parthenolide, a sesquiterpene lactone, to induce apoptosis and cytotoxicity of B-CLL cells in vitro, we cultured these cells in the presence of this substance. Incubations were continued for 3 days. Samples of cells were taken from cultures at 0, 24, 48 and 72 hours to measure apoptosis and cell viability. Peripheral Blood Mononuclear Cells (PBMCs) from five normal donors were submitted to the same techniques and served as control samples. In this study we show for the first time that parthenolide has a potent apoptotic and cytotoxic effect on B-CLL. It is noteworthy that this substance has almost no impact on normal PBMCs. This evidence suggests that parthenolide might be a promising therapy for B-CLL. Keywords: parthenolide – apoptosis – B-CLL INTRODUCTION B-chronic lymphocytic leukemia (CLL) is the most common form of leukemia of adults in the western world (Diehl et al. 1999). This haematological disease represents an example of a human malignancy that appears to result primarily from one or more defects in programmed cell death regu-  Eduardo Mansilla, C.C. 431 La Plata (1900), Provincia de Buenos Aires, Argentina  00-54-221-4787400  edmansil@netverk.com.ar lation mechanisms (Kitada et al. 1998). It is assumed then, following a recent demonstration of a significant increase of the proliferative pool of CLL cells in vivo (Messmer et al. 2005), that the gradual accumulation of the malignant B-CLL cells is mainly the consequence of their selective survival advantages relative to their normal B cell counterparts. As the disease is mainly caused by defective apoptosis, B-CLL should also be a good candidate for treatment by proapoptotic agents. A great diversity of still undefined compounds with antineoplastic properties can be obtained from botanical species. Some of these natural products could be effective in B-CLL by activating different cell death pathways. The active principles of a