ABSTRACT
Bioassay guided isolation of active natural compounds was performed to investigate the anti-tumor potential of the crude extract and isolated compounds from inflorescences of Piper claussenianum. LC-DAD-UV, GC-MS and NMR analyzes revealed the presence of phenolic metabolites in the methanol crude extract. Phytochemical procedures lead to the isolation of the major flavonoids, 2’,6’-dihydroxy-4-methoxychalcone, 5,7- dihydroxyflavanone and 5-methoxy-7-hydroxyflavanone that were assayed for inhibition or viability stimulation of the human breast cancer cell line MCF-7. The results suggest the 2’,6’-dihydroxy-4-methoxychalcone as the biologically active compound in the crude methanol extract of inflorescences from P. claussenianum. The crude extract was found as potential natural source of compounds with breast cancer cell inhibition properties. All isolated compounds have not been described from this species yet.
ABSTRACT
Multidrug resistance to chemotherapy is a major obstacle in the treatment of cancer patients. The best characterised mechanism responsible for multidrug resistance involves the expression of the MDR-1 gene product, P-glycoprotein. However, the resistance process is multifactorial. Studies of multidrug resistance mechanisms have relied on the analysis of cancer cell lines that have been selected and present cross-reactivity to a broad range of anticancer agents. This work characterises a multidrug resistant cell line, originally selected for resistance to the Vinca alkaloid vincristine and derived from the human erythroleukaemia cell K562. This cell line, named Lucena 1, overexpresses P-glycoprotein and have its resistance reversed by the chemosensitisers verapamil, trifluoperazine and cyclosporins A, D and G. Furthermore, we demonstrated that methylene blue was capable of partially reversing the resistance in this cell line. On the contrary, the use of 5-fluorouracil increased the resistance of Lucena 1. In addition to chemotherapics, Lucena 1 cells were resistant to ultraviolet A radiation and hydrogen peroxide and failed to mobilise intracellular calcium when thapsigargin was used. Changes in the cytoskeleton of this cell line were also observed
Subject(s)
Humans , Antineoplastic Agents, Phytogenic/pharmacology , Drug Resistance, Multiple , K562 Cells/drug effects , ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism , Vincristine/pharmacology , Drug Resistance, Multiple/genetics , Gene Expression , Leukemia, Erythroblastic, Acute/drug therapy , ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics , PhenotypeABSTRACT
The present paper summarizes new approaches regarding the progress done to the understanding of the interaction of Trypanosoma cruzi-cardiomyocytes. Mannose receptors localized at the surface of heart muscle cell are involved in binding and uptake of the parasite. One of the most striking events in the parasite-heart muscle cells interaction is the disruption of the actin cytoskeleton. We have investigated the regulation of the actin mRNA during the cytopathology induced in myocardial cells by the parasite. T. cruzi invasion increases calcium resting levels in cardiomyocytes. We have previously shown that Ca2+ ATPase of the sarcoplasmic reticulum (SERCA) is involved in the invasion of T. cruzi in cardiomyocytes. Treating the cells with thapsigargin, a drug that binds to all SERCA ATPases and causes depletion of intracellular calcium stores, we found a 75 per cent inhibition in the T. cruzi-cardiomyocytes invasion.