Flavonoids are products of secondary metabolism of plants. They are present in herbs and trees and also act as natural chemopreventives and anticancer agents. Ligaria cuneifolia (Ruiz & Pav.) Tiegh., Loranthaceae, is a hemiparasite species that belongs to Argentine flora. Phytochemical studies have disclosed the presence of quercetin, catechin-4β-ol and pro-anthocyanidine as polyphenolic compounds in the active extracts. We previously demonstrated that ethyl acetate extract was capable of reducing cell proliferation and inducing apoptotic death of lymphoid tumor cells. The aim of the current study is to determine whether or not catechin, isolated from L. cuneifolia extracts can induce leukemia cell death and to determine its effect on the cytoplasmatic proteins that modulate cell survival. Our results show that catechin can reduce proliferation of murine lymphoma cell line LB02. The effect is mediated by apoptosis at concentrations upper to 100 µg/mL. Cell death is related to the loss of mitochondrial membrane potential (ΔΨm) and a down regulation of survivin and Bcl-2 together with the increase of pro-apoptotic protein Bax. In summary, the current study indicates that catechin present in the extract of L. cuneifolia is in part, responsible for the anti-proliferative activity of whole extracts by induction of ΔΨm disruption and modulation of the anti-apoptotic proteins over expressed in tumor cells. These results give new findings into the potential anticancer and chemopreventive activities of L. cuneifolia.

Apoptosis is a physiological process regulated by a delicate balance be-tween pro and anti-apoptotic factors, which plays a critical role in cell growth. Defects in its balance may lead to a selective advantage in cell survival that promotes neoplasia and malignancy. NFkB enhances cell proliferation thus, the use of selective inhibitors induces apoptosis. The aim of the present study was to characterise the cell line PL104 obtained in this laboratory from bone marrow cells of a young patient with an atypical acute myeloid leukaemia (AML) and to evaluate its susceptibility against the chemotherapeutic agents Doxorubicine (DOX), Vincristine (VCR) Gemcitabine and the inhibitors of NFkB, CAPE and MG-132. PL104 phenotype, evaluated by flow cytometry, showed expression of the following markers: CD19, CD20, CD22, CD38, CD45, CD79a, HLA-DR and lambda chain plus aberrant expression of CD71. The effect of these compounds on cell proliferation was evaluated resulting in 5.2 + 0.7%, 42.8 + 3.6%, 2.4 + 0.4%, 0.7 +0.2% and 0.7 + 0.3% (p < 0.001) of cell growth for DOX (4 µM), VCR (10 µM), Gemcitabina (0.04 µM), CAPE (360 µM) and MG-132 (4 µM) respectively after 24 h of treatment. Apoptosis assessed by acridine orange and ethidium bromide staining after 24 h showed 28.9 + 1.9%, 47 + 2.7%, 77.1 + 5.7% and 92,8 + 2.9% (p < 0.001) for DOX (1.5 µM), VCR (1 µM), CAPE (360 µM) and MG-132 (4 µM) respectively versus 6.63 + 0.2% for untreated cells, data confirmed by Annexin-V test. It can be concluded that the cell line PL104, originated from an AML, corresponds to B lymphocytes significantly susceptible to the chemotherapeutic agents and inhibitors tested. Therefore, NFkB’s implication in controlling these cells’ survival has been demonstrated.

La apoptosis es un proceso fisiológico crítico para el crecimiento celular, regulado por factores pro y anti-apoptóticos. Defectos en su control llevan a una ventaja selectiva en la sobrevida celular favoreciendo el desarrollo de patologías neoplásicas. NFkB puede promover la proliferación celular por lo que el uso de inhibidores selectivos lleva a un aumento de la apoptosis. El objetivo del presente trabajo fue caracterizar la línea celular PL104, obtenida de células de punción de médula ósea de una paciente con diagnóstico de leucemia mieloide aguda (LMA) atípica y evaluar la susceptibilidad de la misma frente a los quimioterápicos Doxorubicina (DOX), Vincristina (VCR), Gemcitabina e inhibidores de NFkB, CAPE y MG-132. El fenotipo evaluado por citometría de flujo resultó positivo para CD19, CD20, CD22, CD38, CD45, CD79a, HLA-DR y cadena lambda con expresión aberrante de CD71. Se verificó el efecto de los agentes mencionados sobre la proliferación celular resultando a las 24 h en un 5.2 + 0.7%, 42.8 + 3.6%, 2.4 + 0.4%, 0.7 + 0.2% y 0.7 + 0.3% (p < 0.001) de sobrevida celular para DOX (4 µM), VCR (10 µM), Gemcitabina (0.04 µM), CAPE (360 µM) y MG-132 (4 µM), respectivamente. La apoptosis evaluada con bromuro de etidio-naranja de acridina para DOX (1.5 µM), VCR (1 µM), CAPE (360 µM) y MG-132 (4 µM) a las 24 h fue de 28.9 + 1.9%, 47 + 2.7%, 77.1 + 5.7% y 92,8 + 2.9% (p < 0.001) respectivamente vs. 6.6 + 0.2% para las células sin tratar, datos confirmados por Annexin-V. Se concluye que la línea PL104 derivada de una LMA corresponde a linfocitos B sensibles tanto a la acción de los quimioterápicos testeados como a los inhibidores de NFkB, lo que indica la implicancia de dicho factor en la sobrevida de estas células.