title: Caffeic Acid Phenylethyl Ester and MG-132 Have Apoptotic and Antiproliferative Effects on Leukemic Cells But Not on Normal Mononuclear Cells.
abstract: Chemotherapy aims to limit proliferation and induce apoptotic cell death in tumor cells. Owing to blockade of signaling pathways involved in cell survival and proliferation, nuclear factor kappaB (NF-kappaB) inhibitors can induce apoptosis in a number of hematological malignancies. The efficacy of conventional chemotherapeutic drugs, such as vincristine (VCR) and doxorubicine (DOX), may be enhanced with combined therapy based on NF-kappaB modulation. In this study, we evaluated the effect of caffeic acid phenylethyl ester (CAPE) and MG-132, two nonspecific NF-kappaB inhibitors, and conventional chemotherapeutics drugs DOX and VCR on cell proliferation and apoptosis induction on a lymphoblastoid B-cell line, PL104, established and characterized in our laboratory. CAPE and MG-132 treatment showed a strong antiproliferative effect accompanied by clear cell cycle deregulation and apoptosis induction. Doxorubicine and VCR showed antiproliferative effects similar to those of CAPE and MG-132, although the latter drugs showed an apoptotic rate two-fold higher than DOX and VCR. None of the four compounds showed cytotoxic effect on peripheral mononuclear cells from healthy volunteers. CAPE- and MG-132-treated bone marrow cells from patients with myeloid and lymphoid leukemias showed 69% (P < .001) and 25% decrease (P < .01) in cell proliferation and 42% and 34% (P < .01) apoptosis induction, respectively. Overall, our results indicate that CAPE and MG-132 had a strong and selective apoptotic effect on tumor cells that may be useful in future treatment of hematological neoplasias.
authors.affiliation: Instituto de Estudios de la Inmunidad Humoral "Prof. Ricardo A. Margni," CONICET, Departamento de Inmunología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Victoria
authors.initials: V
authors.lastname: Cavaliere
authors.forename: Daniela L
authors.initials: DL
authors.lastname: Papademetrio
authors.forename: Mario
authors.initials: M
authors.lastname: Lorenzetti
authors.forename: Pamela
authors.initials: P
authors.lastname: Valva
authors.forename: María Victoria
authors.initials: MV
authors.lastname: Preciado
authors.forename: Patricia
authors.initials: P
authors.lastname: Gargallo
authors.forename: Irene
authors.initials: I
authors.lastname: Larripa
authors.forename: Mariela B
authors.initials: MB
authors.lastname: Monreal
authors.forename: María Laura
authors.initials: ML
authors.lastname: Pardo
authors.forename: Silvia E
authors.initials: SE
authors.lastname: Hajos
authors.forename: Guillermo Ac
authors.initials: GA
authors.lastname: Blanco
authors.forename: Elida Mc
authors.initials: EM
authors.lastname: Alvarez