[Chronic lymphoid B-cell leukemia].
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Biomedical subjects
Publications and source records attributed to C Salanoubat.
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Extracts of the plant St John's wort, Hyperforin perforatum L., have been used for centuries in traditional medicine, notably for the treatment of depression. One of their main lipophilic components, a natural prenylated phloroglucinol termed hyperforin (HF), has been identified as the major molecule responsible for the antidepressant effects of this plant. Within the last few years, a number of studies have demonstrated that HF displays, in addition, several other biological properties of potential pharmacological interest. They include an antibacterial capacity and inhibitory effects on inflammatory mediators. It is worth noting that HF also promotes apoptosis of various cancer cells from solid tumors and hematological malignancies, including B-cell chronic lymphocytic leukemia. In addition, HF inhibits the capacity of migration and invasion of different tumor cells, as well as exhibiting antiangiogenic effects. Altogether, these properties qualify HF as a lead structure for the development of new therapeutic molecules in the treatment of various diseases, including some malignant tumors.
The effects of the hyperforin (HF), a natural phloroglucinol purified from Hypericum perforatum, were investigated ex vivo on leukemic cells from patients with B-cell chronic lymphocytic leukemia (B-CLL). HF was found to promote apoptosis of B-CLL cells, as shown by time- and dose-dependent stimulation of phosphatidylserine externalization and DNA fragmentation, by disruption of the mitochondrial transmembrane potential, caspase-3 activation and cleavage of the caspase substrate PARP-1. Moreover, HF-induced downregulation of Bcl-2 and Mcl-1, two antiapoptotic proteins that control mitochondrial permeability. HF also downregulated two proteins which are overexpressed by B-CLL patients' cells, the cell cycle inhibitor p27kip1 through caspase-dependent cleavage into a p23 form, and the nitric oxid (NO) synthase of type 2 (inducible NO synthase). This latter was accompanied by reduction in the production of NO known to be antiapoptotic in B-CLL cells. Preventing effects of the general caspase inhibitor z-VAD-fmk indicated that HF-promoted apoptosis of B-CLL cells was mostly caspase dependent. Furthermore, normal B lymphocytes purified from healthy donors appeared less sensitive to HF-induced apoptosis than B-CLL cells. These results indicate that HF may be of interest in the development of new therapies for B-CLL based on the induction of apoptosis and combination with cell cycle-dependent antitumor drugs.
Mantle cell lymphomas are characterized by a male predominance with a range between 55 and 65 years (sex ratio M/F of 6.5). When the sex ratio of patients having mantle cell lymphoma was compared to that of each of the subtypes of non-Hodgkin's lymphomas, it was significantly higher in all cases except Burkitt's and lymphoblastic T-cell lymphomas. These observations suggest a possible relation between the chromosome X and mantle cell lymphomas which has to be explored.