Abstract Different solvent extracts from Aphanothece halophytica (A. halophytica) were evaluated for their cytotoxic effects against four human cancer cell lines. The samples demonstrated different percentages of cyanobacteria species populations. The samples containing 100% A. halophytica and 90% A. halophytica showed a significant cytotoxic effect in human breast cancer cells MDA231. The cytostatic effect was demonstrated in MDA231 and human glioblastoma T98G cells regardless of the treatment, resulting in a significant cell cycle arrest in the S phase. The chemical profiles of the extracts were proven to be diverse in qualitative and quantitative compositions. This variability was dependent on the A. halophytica´s abundance in each extract. The 100% A. halophytica extract induced cytotoxic and cytostatic effects in breast cancer cells, and those could be associated with the predominance of fatty acids, hydrocarbons and phthalates, indicating that A. halophytica is an interesting source of novel compound with anticancer effect.

A resistência a múltiplos fármacos é o principal obstáculo no tratamento de pacientes com câncer. O mecanismo responsável pela resistência múltipla mais bem caracterizado envolve a expressão do produto do gene MDR-1, a glicoproteína P. Entretanto, o processo de resistência tem fatores múltiplos. Estudos de mecanismos de resistência múltipla a fármacos têm dependido da análise de linhagens celulares tumorais que foram selecionadas e apresentam reatividade cruzada a uma ampla faixa de agentes anti-tumorais. Este trabalho caracteriza uma linhagem celular com múltipla resistência a fármacos, selecionada originalmente pela resistência ao alcalóide de Vinca vincristina e derivado da linhagem eritro-leucêmica K562. Esta linhagem celular, denominada Lucena 1, super-expressa a glicoproteína P e tem sua resistência revertida pelos quimio-sensibilizantes verapamil, trifluoperazina e ciclosporinas A, D e G. Ademais, demonstramos que o azul de metileno era capaz de reverter parcialmente a resistência nesta linhagem celular. Em contraste, o uso de 5-flúor-uracil aumentava a resistência de Lucena 1. Adicionalmente aos quimioterápicos, células Lucena 1 eram resistentes radiação ultra-violeta A e peróxido de hidrogênio e deixavam de mobilizar o cálcio intra-celular quando se usava tapsigargina. Mudanças no cito-esqueleto desta linhagem foram também observadas.

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.