Antitumor screening of Pterodon pubescens terpenic fraction indicates high sensitivity for lymphocytic leukemia cells.

Cancer is the second leading cause of human mortality worldwide. Therefore, the search for new drugs or alternative therapy strategies has been required. Anticancer agents have been developed from plants since the 1950s and natural products still represent an important source of new and promising bioactive molecules. This work describes the cytotoxic effects of SF5 on tumor cells of high prevalence in the world and investigated some mechanisms of its antitumor action. The antitumor screening was performed with human lung carcinoma (A549), human breast (MCF-7) and prostate (PC-3) adenocarcinoma and chronic myeloid and acute lymphocytic leukemia cell lines. The acute lymphocytic leukemia Jurkat cells presented high sensitivity to the cytotoxic effects of SF5 (inhibition of 85-90%), compared with either the chronic myeloid leukemia K562 or solid tumor cell lines (lung, breast and prostate). SF5 arrested the cell cycle in G1 phase, which may be related with the observed downregulation of mRNA expression of c-Myc transcription factor at 24 h and 36 h. SF5 treatment induced cytochrome c release from mitochondria to cytosol, leading the Jurkat cells into apoptosis, which was evidenced by the internucleosomal fragmented DNA and increased number of annexin V-FITC positive cells. The SF5 showed high cytotoxicity for lymphocytic leukemia cells and low or none for solid tumor cells, without toxicity for peripheral mononuclear cells of healthy humans. SF5 altered gene expression, arrested the cell cycle and induced apoptosis via the mitochondrial pathway, similar to traditional antineoplastic chemotherapeutic drugs.

A modified assay for measuring thymocyte co-stimulatory activity

The observation that murine thymocytes increase their proliferation to interleukin 1 (IL-1) in the presence of phytohemagglutinin (PHA) when pre-incubated with interleukin 2 (IL-2) allowed the introduction of a modified assay for the measurement of IL-1 or the search of thymocyte-inducing proliferative activities in biological samples. Pre-incubation of thymocytes for 24 hr with 50 u/ml IL-2, followed by washings, elicited their maximal response to IL-1 in the usual lymphocyte activating factor (LAF) assay. This suggests that sequential events lead to thymocyte activation. The responsiveness is three to five fold greater than, and the total time of assay is the same as that of the LAF assay. Interestingly, pre-incubation with IL-2 renders thymocytes more sensitive than responsive to crude monocyte conditioned media. The use of the MTT colorimetric method for the assessment of thymocyte proliferation, and of the lectin jacalin as a co-mitogen are suggested as alternatives to be used in co-stimulatory assays

Hematopoese: I. Citocinas envolvidas em sua regulaçäo / Hematopoiesis: I. Cytokines involved in its regulation

O estudo da participaçäo direta de citocinas, tais como os fatores estimuladores do crescimento de colônias, as interleucinas, e outros, no controle das etapas da hematopoese, vem sendo prejudicado pela presença in vitro de células näo-hematopoéticas, capazes de intermediar os efeitos das citocinas sobre os precursores hematopoéticos. Recentemente pôde-se verificar que o antígeno CD34 se expressa na membrana de essencialmente todas as células pluripotenciais, mas näo da maioria das células diferenciadas do sangue ou do estroma da medula óssea, o que veios a permitir experimentos in vitro com populaçöes ricas em células pluripotenciais, purificadas com base na expressäo deste antígeno. Tais experimentos permitiram uma reavaliaçäo dos resultados obtidos previamente com populaçöes menos puras e ampliaram o conhecimento sobre a participaçäo das diferentes citocinas nos processos de diferenciaçäo das distintas linhagens hematopoéticas, tema desta revisäo. O papel de interferons, fatores necrosantes de tumor e fatores de transformaçäo de crescimento ß na regulaçäo negativa da hematopoese säo também analisados