Upregulation of miR-129-5p increases the sensitivity to Taxol through inhibiting HMGB1-mediated cell autophagy in breast cancer MCF-7 cells

Although Taxol has improved the survival of cancer patients as a first-line chemotherapeutic agent, an increasing number of patients develop resistance to Taxol after prolonged treatment. The potential mechanisms of cancer cell resistance to Taxol are not completely clear. It has been reported that microRNAs (miRNAs) are involved in regulating the sensitivity of cancer cells to various chemotherapeutic agents. In this study, we aimed to explore the role of miR-129-5p in regulating the sensitivity of breast cancer cells to Taxol. Cell apoptosis and autophagy, and the sensitivity of MCF-7 cells to Taxol were assessed with a series of in vitro assays. Our results showed that the inhibition of autophagy increased the Taxol-induced apoptosis and the sensitivity of MCF-7 cells to Taxol. Up-regulation of miR-129-5p also inhibited autophagy and induced apoptosis. Furthermore, miR-129-5p overexpression increased the sensitivity of MCF-7 cells to Taxol. High mobility group box 1 (HMGB1), a target gene of miR-129-5p and a regulator of autophagy, was negatively regulated by miR-129-5p. We found that interference of HMGB1 enhanced the chemosensitivity of Taxol by inhibiting autophagy and inducing apoptosis in MCF-7 cells. Taken together, our findings suggested that miR-129-5p increased the chemosensitivity of MCF-7 cells to Taxol through suppressing autophagy and enhancing apoptosis by inhibiting HMGB1. Using miR-129-5p/HMGB1/autophagy-based therapeutic strategies may be a potential treatment for overcoming Taxol resistance in breast cancer.

Screening of endophytic fungi stored in a culture collection for taxol production.

In this work, four isolates of endophytic fungi (Alternaria alternata, Colletotrichum gloesporioides, Glomerella cingulata and Nigrospora sphaerica), deposited in the culture collection 'University Recife Mycologia' (URM) at the Universidade Federal de Pernambuco, were characterized for the genes ITS 1 and 4 (region 5.8 S) and evaluated for taxol production.

Screening of endophytic fungi stored in a culture collection for taxol production

In this work, four isolates of endophytic fungi (Alternaria alternata, Colletotrichum gloesporioides, Glomerella cingulata and Nigrospora sphaerica), deposited in the culture collection ‘University Recife Mycologia (URM) at the Universidade Federal de Pernambuco, were characterized for the genes ITS 1 and 4 (region 5.8 S) and evaluated for taxol production.(AU)

Screening of endophytic fungi stored in a culture collection for taxol production

Abstract In this work, four isolates of endophytic fungi (Alternaria alternata, Colletotrichum gloesporioides, Glomerella cingulata and Nigrospora sphaerica), deposited in the culture collection University Recife Mycologia (URM) at the Universidade Federal de Pernambuco, were characterized for the genes ITS 1 and 4 (region 5.8 S) and evaluated for taxol production.

Screening of endophytic fungi stored in a culture collection for taxol production

Abstract In this work, four isolates of endophytic fungi (Alternaria alternata, Colletotrichum gloesporioides, Glomerella cingulata and Nigrospora sphaerica), deposited in the culture collection 'University Recife Mycologia' (URM) at the Universidade Federal de Pernambuco, were characterized for the genes ITS 1 and 4 (region 5.8 S) and evaluated for taxol production.

Effect of the association of 1-methyl-DL-tryptophan with paclitaxel on the expression of indoleamine 2,3-dioxygenase in cultured cancer cells from patients with breast cancer.

Breast cancer is the most common type of cancer among women and the survival of patients affected by it is increasing, mainly due to several new approaches in early diagnosis and more effective treatments. The enzyme indoleamine 2,3-dioxygenase (IDO) is expressed in many cells, including tumor cells. IDO acts by inhibiting the proliferation of T lymphocytes, thus compromising their cytotoxic activity. 1-Methyl-DL-tryptophan (1MT) is a competitive inhibitor of IDO, which blocks its immunosuppressive effect. Paclitaxel is an antineoplastic drug largely used in breast cancer therapy. Thus, this study aimed to determine the in vitro effect of the association of 1MT and paclitaxel chemotherapy, as an approach to reduce tumor growth. It is believed that this would allow the restoration of T lymphocyte proliferation capability and its cytotoxic response. The supplemented cultures showed that the most significant differences in the expression of IDO were observed in the group treated with paclitaxel associated with 1-MT continuous supplementation, reducing enzyme expression from 12.06 to 3.56 %. This association was more effective in reducing IDO expression and could collaborate in developing a new therapeutic strategy for breast cancer treatment.

Una revisión sobre la producción de taxoides anticancerígenos en cultivos in vitro de callos y células de Taxus spp / A review on the production of taxoids anti-cancer of callus and cells of Taxus spp. in cultures in vitro

Los taxoides son diterpenos polioxigenados provenientes de la ruta metabólica del 2-metil-eritritol 4-fosfato cuya biosíntesis se genera en los plastidios. La importancia de los taxoides entre ellos el taxol, en el área de la medicina humana es muy valiosa debido a la utilización en oncología, fármaco utilizado contra el cáncer de seno, pulmón y ovario. Las especies de árboles de Taxus spp. están en peligro de extinción debido a la tala inmoderada, a la baja reproducción, lento crecimiento; por lo que el cultivo de tejidos vegetales in vitro es una alternativa biotecnológica de alto impacto y de gran ayuda para el conocimiento de la producción de los taxoides a nivel in vitro y sobre todo, para la conservación de este valioso recurso natural. Los objetivos de este artículo son: origen del taxol, su mecanismo de acción biológico, la biosíntesis de los taxoides, el método de extracción así como la producción de taxoides in situ y en cultivos in vitro de callos y células de Taxus spp.

The taxoids are polioxigenated diterpenes from the metabolic pathway of the 2-methyl-erythritol 4-phosphate whose biosynthesis is generated in the plastides. The importance of the taxoides including taxol, in the area of human medicine is very valuable due to the use in oncology, drug used against breast, lung and ovarian cancer. The species of trees of Taxus spp. are in danger of extinction due to logging immoderate, to the low reproduction rate, slow growth; therefore, the plant tissue culture in vitro is a biotechnological alternative high-impact and a great help to the knowledge of the production of the taxoides to level in vitro and above all, for the conservation of this valuable natural resource. The objectives of this article are to determine some general information about the geographical distribution of Taxus spp.; chemical characteristics of taxoids, biological mechanism of action of taxol; path of biosynthesis, methods of extraction and analysis of the taxoids and a current review of the production of taxoids in situ and in vitro cultures and cells of Taxus spp.

Thermodynamics of molecular recognitions between antineoplastic drug taxol and phosphatidylcholine

The aim of this study was to study the basic features of Taxol recognition with phospholipids by applying the thermodynamic and spectroscopic measurements. The obtained information could be used further for deductions on its precise cellular and pharmacological mechanisms of action, on improvements of its solubility properties by phospholipids, as well as for designing the novel lipidic carriers for drug delivery.

Modeling for Taxol® Separation in a simulated moving bed

This work presents an alternative numerical resolution strategy for a model to describe the dynamic of linear adsorption processes involving multicomponent mixture of taxanes with Taxol® (paclitaxel), a powerful anti-cancer agent, and non-identified impurities, in a Simulated Moving Bed (SMB) system. To solve the model, a hybrid method were used. The liquid concentration inside the particles was found analytically and was related with the liquid bed concentration using Duhamel's theorem. The results from simulation were compared with experimental ones from the literature, showing a good agreement, which demonstrated the applicability of the model and of the hybrid resolution proposed.

O Taxol® , conhecido também como Paclitaxel, é uma droga poderosa utilizada no tratamento de câncer. Quanto à sua obtenção, o Taxol® pode ser recuperado a partir de um meio líquido cultivado, oriundo da cultura de células vegetais. Entretanto, o Taxol® existe em mistura com um número alto de taxanas estruturalmente semelhantes a ele, o que leva a dificuldade em recuperá-lo. Uma das estratégias tecnológicas mais recentes para este tipo de situação é o emprego de sistemas cromatográficos contínuos conhecidos como Leito Móvel Simulado (LMS). O LMS caracteriza-se por provocar o aparente escoamento contínuo em contracorrente entre a fase líquida e o leito sólido, aumentando a força motriz necessária para transferência de massa e, consequentemente, a eficiência do processo. Dessa maneira, o objetivo deste trabalho é o de apresentar um modelo matemático e a sua solução visando à separação de Taxol® (Paclitaxel) de uma mistura de taxanas. O método matemático proposto é híbrido, em que a fase estacionária é resolvida analiticamente, enquanto a fase móvel, via resolução numérica, sendo ambas as fases interconectadas pelo teorema de Duhamel. Os resultados oriundos da solução numérica foram comparados com aqueles experimentais encontrados na Literatura, demonstrando desempenho bastante favoráveis para o modelo e métodos de solução propostos.

Giardia lamblia: distribuição de microtúbulos no citoesqueleto de trofozoítos e cistos utilizando taxóide fluorescente / Giardia lamblia: distribution of microtubules on the cytoskeleton of trophozoites and cysts by use of fluorescent taxoid

Giardia lamblia é um protozoário parasito do intestino delgado, agente etiológico da giardiose, o qual apresenta um complexo citoesqueleto composto por microtúbulos. Neste estudo, a distribuição dos microtúbulos no citoesqueleto de trofozoítos e cistos de G. lamblia foi investigada por meio de um taxóide fluorescente, o FLUTAX-2 - um derivado do Taxol que se liga aos dímeros polimerizados de alfabeta-tubulina. O efeito do metronidazol sobre o citoesqueleto do organismo também foi avaliado. FLUTAX-2 foi capaz de se ligar aos microtúbulos de trofozoítos e cistos de G. lamblia, tornando possível a visualização de estruturas do citoesqueleto do microrganismo, como flagelos, funis e disco adesivo. Além disso, FLUTAX-2 marcou os trofozoitos cultivados por diferentes períodos, revelando que o intervalo de 48 horas é o melhor tempo de cultivo. A incubação dos parasitos na presença de metronidazol não demonstrou alteração significativa na marcação microtubular por FLUTAX-2. Nosso grupo já apresentou a marcação pelo FLUTAX-2 em outros protozoários, Trichomonas vaginalis, T. gallinae e Tritrichomonas foetus, e este é o primeiro trabalho a revelar o perfil de ligação em G. lamblia. Os resultados contribuem para o conhecimento de aspectos biológicos e morfológicos do parasito e sugerem perspectivas para o diagnóstico laboratorial da giardiose.

G. lamblia is a protozoan parasite of the small intestine and the etiologic agent ofgiardiosis, which presents a complex cytoskeleton composed of microtubules. In this study, the microtubule cytoskeleton was labeled in trophozoites and cysts of G. lamblia, using a fluorescent taxoid (FLUTAX-2), a derivative of Taxol, which binds to áâ-tubulin dimer polymerized. In addition, the effect of metronidazole on the cytoskeleton of the parasite was also evaluated. FLUTAX-2 was able to labelthe microtubules of trophozoites and cysts, allowing the observation of cytoskeletal structures, such as flagella, funis, adhesive disk, and median body. Moreover, FLUTAX-2 labeled the trophozoites from several different cultivation times, revealing the 48 hours as the best incubation period. The incubation of parasites in presence of metronidazole did not show significant alteration on the microtubulelabeling by FLUTAX-2. We have shown the FLUTAX-2 labeling in other protozoa,Trichomonas vaginalis, T. gallinae and Tritrichomonas foetus, and this is the first report revealing the binding profile in G. lamblia. Our results contribute to the knowledge of biological and morphological features of this intestinal pathogen. Furthermore, our data showed no modification of microtubule profile labeling in presence of metronidazole. Finally, a new perspective for giardiosis diagnosticis suggested, since trophozoites and cysts of G. lamblia were labeled withFLUTAX-2.