Pro-Apoptotic Antitumoral Effect of Novel Acridine-Core Naphthoquinone Compounds against Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) is a global public health problem with high incidence and mortality. The chemotherapeutic agents used in the clinic, alone or in combination, usually lead to important side effects. Thus, the discovery and development of new antineoplastic drugs are essential to improve disease prognosis and reduce toxicity. In the present study, acridine-core naphthoquinone compounds were synthesized and evaluated for their antitumor activity in OSCC cells. The mechanism of action, pharmacokinetics, and toxicity parameters of the most promising compound was further analyzed using in silico, in vitro, and in vivo methods. Among the derivatives, compound 4e was highly cytotoxic (29.99 µM) and selective (SI 2.9) at levels comparable and generally superior to chemotherapeutic controls. Besides, compound 4e proved to be non-hemolytic, stable, and well tolerated in animals at all doses tested. Mechanistically, compound 4e promoted cell death by apoptosis in the OSCC cell, and molecular docking studies suggested this compound possibly targets enzymes important for tumor progression, such as RSK2, PKM2, and topoisomerase IIα. Importantly, compound 4e presented a pharmacological profile within desirable parameters for drug development, showing promise for future preclinical trials.

[Have you eaten any DNA today? Science communication during Science and Technology Week in Brazil]. / Você já comeu DNA hoje? Divulgação científica durante a Semana da Ciência e Tecnologia no Brasil.

During the first National Science and Technology Week held in 2004, science centers and museums, universities and schools engaged in activities with the idea of divulging science to the people. Demonstrations of the extraction of DNA from fruits were conducted in supermarkets in 11 Brazilian cities by two institutions, DNA Vai à Escola and Conselho de Informação e Biotecnologia. This article describes the formation of a national network of people interested in communicating information about genetics to the lay public and the implementation of a low-cost science communication activity in different parts of the country simultaneously. It also analyzes the impact caused by this initiative and the perceptions of those involved in its organization.

Voce ja comeu DNA hoje? Divulgacao cientifica durante a Semana da Ciencia e Tecnologia no Brasil / Have you eaten any DNA today? Science communication during Science and Technology Week in Brazil

Durante a Primeira Semana Nacional de Ciências e Tecnologia, em 2004, centros e museus de ciência, universidades e escolas implementaram atividades com o objetivo de divulgar ciência para a população. O DNA Vai à Escola se juntou ao Conselho de Informação e Biotecnologia e praticou a extração de DNA de frutas em supermercados de 11 cidades brasileiras. Este artigo descreve a formação da rede nacional de pessoas interessadas em transmitir informações sobre genética para o público leigo e a implementação de uma atividade de divulgação científica de baixo orçamento em vários pontos do país, simultaneamente. Apresenta ainda o impacto causado pela atividade e as percepções daqueles envolvidos na sua organização.

During the first National Science and Technology Week held in 2004, science centers and museums, universities and schools engaged in activities with the idea of divulging science to the people. Demonstrations of the extraction of DNA from fruits were conducted in supermarkets in 11 Brazilian cities by two institutions, DNA Vai à Escola and Conselho de Informação e Biotecnologia. This article describes the formation of a national network of people interested in communicating information about genetics to the lay public and the implementation of a low-cost science communication activity in different parts of the country simultaneously. It also analyzes the impact caused by this initiative and the perceptions of those involved in its organization.

Estudo do papel de galectina-3 no fenótipo maligno de células de melanoma primário e metastático / Galectin-3 supports the malignant phenotype of vertical growth phase melanomas

Galectina-3 (Gal-3) é uma proteína com atividades pleiotrópicas expressa em uma grande variedade de células e tecidos. Suas diversas atividades variam de acordo com o compartimento celular em que esta é encontrada. Estudos recentes demonstram que a expressão e distribuição intracelular de Gal-3 em melanoma está correlacionada com a progressão tumoral. .... O silenciamento de Gal-3 nas células WM793 é acompanhado da diminuição da ativação de AKT e o aumento da expressão de proteínas pró-apoptóticas. Concomitantemente, é observado o aumento da expressão de p16 e hipofosforilação de Rb. Análises por microscopia confocal demonstram que Gal-3 co-localiza com β-catenina em células de melanoma e que o silenciamento de Gal-3 diminui a presença de β-catenina nuclear. Entretanto, em melanócitos e células de crescimento radial, a ausência de Gal-3 nuclear não impede a distribuição nuclear de β-catenina. Os dados apresentados aqui indicam que Gal-3 possui um papel crucial em melanomas de crescimento vertical. O silenciamento de Gal-3 não parece ser suficiente para afetar melanomas metastáticos, que possivelmente adquirem estratégias complementares de sobrevivência para o escape de mecanismos supressores de tumor.

Galectin-3 (Gal-3) is a pleiotropic protein expressed in a variety of tissues. It has diverse activities that are contingent upon its subcellular localization Previous studies have demonstrated that Gal-3 expression and subcellular distribution is correlated to melanoma progression. Here, the effects of Gal-3 depletion were investigated in melanoma cells derived from different stages of tumor progression using lentiviral shRNA. Gal-3-deficient (shGal-3) vertical growth phase (WM793) melanoma cells displayed altered cell morphology, impaired growth in soft agar, as well as reduced invasiveness. Tumor growth in NOD/SCID mice injected subcutaneously with WM793 shGal-3 was dramatically affected. Interestingly, shGal-3 caused no phenotypic changes in metastatic melanoma cells. Impaired AKT activation and upregulation of pro-apoptotic proteins were detected, as well as upregulation of p16 and hipophosphorilation of Rb. Immunofluorescence analyses demonstrated that Gal-3 and ß-catenin co-localize, and that Gal-3 knockdown caused decreased nuclear ß-catenin localization. However the absence of nuclear Gal-3 in melanocytes and RGP melanoma cells do not affect nuclear ßcatenin distribution. Together, these data demonstrate that Gal-3 has a crucial role in VGP melanoma. Furthermore, Gal-3 depletion is not sufficient to affect metastatic cells, which likely develop complementary survival strategies to escape tumor suppressive mechanisms.