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6-(METHYLSULFINYL) HEXYL ISOTHIOCYANATE AS POTENTIAL CHEMOPREVENTIVE AGENT: MOLECULAR AND CELLULAR PROFILE IN LEUKEMIA CELL LINES
No full text6-(Methylsulfonyl) hexyl isothiocyanate as potential chemopreventive agent: molecular and cellular profile in leukaemia cell lines
Full text linkNumerous laboratory and epidemiological studies show that the risk of developing several types of cancer can be reduced with the employment of natural substances that act with multiple mechanisms. In this context, an important role is played by the isothiocyanates. Recently, 6-(methylsulfonyl)hexyl isothiocyanate (6-MITC), present in the root of Wasabia Japonica, has stimulated the interest of researchers as a chemopreventive agent. In this particular study we have focused on evaluating 6-MITC’s in vitro cytotoxic, cytostatic and cytodifferentiating activities, as well as its pro-apoptotic potential. These effects were investigated by way of flow cytometric analysis of Jurkat and HL-60 cells as well as of healthy lymphocytes extracted from the blood of AVIS donors, in order to verify a potential selectivity of action. The results demonstrate that 6-MITC exerts a stronger cytotoxic effect on tumour cells than on healthy cells. The apoptosis induction exerted by 6-MITC on transformed cells is triggered by an extrinsic pathway, as demonstrated by the statistically significant increase in the percentage of cells with activated caspase-8. It was also observed that 6-MITC is able to limit tumour growth by slowing down and blocking the cell cycle of Jurkat and HL-60 cells respectively, in a dose- and time-related manner, while exerting no activity of any kind on the replication of healthy cells. Finally, by measuring the expression levels of CD-14 and CD-15, 6-MITC showed the ability to induce cytodifferentiation of HL-60 cells into macrophage and granulocytic phenotypes
6-(Methylsulfonyl) hexyl isothiocyanate induce autophagy in leukemia cell lines
No full textIntroduction: Autophagy is a fundamental catabolic process of cellular survival through which the cell degrades and recycles cellular components. However, the alteration of its normal mechanism may be responsible for the development of many diseases, such as cancer. The role of autophagy in cancer is extremely complex; on the one hand, in the early stages of neoplastic transformation it can act as a tumor suppressor avoiding the accumulation of proteins, damaged organelles and reactive oxygen species; on the other hand, during the advanced stage of cancer, autophagy is exploited by cancer cells to survive under starved.
Numerous substances of natural origin have been shown to have chemopreventive activity and in particular, isothiocyanates are of great interest, between these, more recently the 6-(Methylsulfonyl) hexyl isothiocyanate (6-MITC) attracted the attention of researchers.
Studies conducted in our laboratories and recently published demonstrating that 6-MITC is able to exhibit cytotoxic, cytostatic, and cytodifferentiation effects on different leukemic cell lines. These encouraging results stimulate us to continue research investigating other possible potentials. In this context it is extremely interesting to evaluate the modulation of the autophagic process by 6-MITC and the related pathways, with particular attention to ROS-autophagy-cancer interconnection.
Materials and Methods: Flow cytometric analysis of Jurkat and HL-60 cells treated with 6-MITC 0-8 M and 0-16M respectively for 20h allowed to evaluate the autophagy mechanism. Subsequently, to better characterize the interconnection between autophagy and oxidative stress the level of DCF, MitoPY, HE, MitoSOX, DHR123, MBC were also evaluated.
At the end, in order to extended us previous experience, the data has been confirmed through InCell Analyzer 2000.
Results: 6-MITC induced autophagy in Jurkat and HL-60 cells at the highest concentration tested.
The levels of intracellular hydrogen peroxide (DCF) increase in a dose dependent manner in both cells line while the levels of mitochondrial hydrogen peroxide (MitoPY) only in HL-60. For the other markers no statistically significant increase was observed.
Conclusion: Our data suggest that 6-MITC might be considered an interesting chemopreventive agent. The isothiocyanate is able to induce autophagy through ROS generation and in particular through the production of hydrogen peroxide. These first results encourage the conduct of further studies to learn more about the interconnection oxidative stress, autophagy and cancer
6-(Metilsulfonil) esil isotiocianato come potenziale agente chemiopreventivo: profilo molecolare e cellulare in linee cellulari leucemiche
No full textNumerosi studi epidemiologici e ricerche di laboratorio dimostrano come il rischio di sviluppare diversi tipi di tumori può essere ridotto mediante l'utilizzo di sostanze naturali che agiscono attraverso diversi meccanismi d’azione. In questo contesto, un ruolo importante è giocato dagli isotiocianati e, più recentemenre, il 6-(metilsulfonil)-esil isotiocianato (6-MITC), un isotiocianato presente nel rizoma della Wasabia Japonica, ha stimolato l'interesse dei ricercatori come potenziale agente chemiopreventivo.
In questo particolare studio ci siamo concentrati sulla valutazione delle attività citotossiche, citostatiche e citodifferenziative in vitro del 6-MITC, così come il suo potenziale pro-apoptotico. Questi effetti sono stati analizzati mediante citofluorimetria a flusso su una linea umana di leucemia linfoblastica (Jurkat) e una linea umana di leucemia promielocitica acuta umana (HL-60) e su linfociti sani, estratti dal sangue periferico di donatori AVIS, al fine di valutare una potenziale selettività di azione. I risultati dimostrano che il 6-MITC esercita un effetto citotossico più potente sulle cellule tumorali che sulle cellule sane. In particolare, l'induzione di apoptosi indotta dal 6-MITC sulle cellule trasformate avviene tramite attivazione della sola via estrinseca, come dimostrato dall’aumento statisticamente significativo della percentuale di cellule con caspasi-8 attiva. È stato inoltre osservato che il 6-MITC è in grado di limitare la crescita tumorale rallentando e bloccando il ciclo cellulare delle cellule Jurkat e HL-60 rispettivamente, in maniera dose e tempo correlata, senza esercitare alcun effetto sulla replicazione delle cellule sane. Infine, misurando i livelli di espressione di CD-14 e CD-15, il 6-MITC si è mostrato in grado di indurre citodifferenziazione delle cellule HL-60 sia verso il fenotipo macrofagico che granulocitico rispettivamente
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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