Selection of new molecules and treatment modalities to fight cancer

O c??ncer ?? uma das principais causas de morte no mundo, onde os ??ndices devem aumentar 50% at?? 2020. Embora a ressec????o cir??rgica e terapias adicionais (como a quimioterapias e radioterapias) sejam capazes de curar tumores prim??rios bem delimitados, o mesmo n??o se aplica a met??stase devido ao seu envolvimento sist??mico e a resist??ncia a terapias convencionais. Portanto, atualmente o desfio cl??nico ?? desenvolver novas drogas e modalidades de tratamentos que ir??o impactar significativamente as taxas de cura do c??ncer. Neste sentido, o presente trabalho objetivou avaliar o efeito antineopl??sico e investigar a rota de apoptose induzido pelo disseleneto de diarila e seus derivados substitu??dos - (4-ClC6H4Se)2, (3-CF3C6H4Se)2 e (4-MeOC6H4Se)2 - em c??lulas de adenocarcinoma de colorretal humano (HT-29). Verificamos que os compostos (3-CF3C6H4Se)2 e (4-MeOC6H4Se)2 induziram um efeito citotoxidade por meio de apoptose, onde os genes pr??-apoptoticos (Bax, caspase-9, caspase-8, fator indutor de apoptose (AIF) e endonuclease G (EndoG)) foram altamente expressos e os genes anti-apopt??tico (Bcl-2 e survivin) mostraram uma redu????o na sua express??o. Em um segundo momento avaliamos o potencial antineopl??sico das lectinas Canavalia brasiliensis (ConBr), Canavalia boliviana (ConBol) e Canavalia ensiformis (ConA) em c??lulas HT-29, as quais se mostraram efetivas em reduzir a viabilidade celular. Uma vez confirmado o efeito antineopl??sico, as lectinas forma marcadas com FITC e a sua intera????o com as c??lulas tumorais foi investigado. As lectinas FITC-ConA e FITC-ConBol demonstraram potencial de se ligar as c??lulas HT-29 ao contr??rio da FITC-ConBr. A fim de investigar uma nova modalidade de tratamento foi avaliada a intera????o entre as respectivas lectinas com as c??lulas HT-29 quando associadas ?? nanotubos de carbonos funcionalizados de paredes m??ltiplas (f-MWCNTs). Quando os f-MWCNTs foram incorporados as lectinas FITC-ConA e FITC-ConBol houve um aumentaram na intensidade de fluoresc??ncia.Cancer is a leading cause of death and its rates are expected to increase 50% by 2020. Although surgical resection and additional therapies (such as chemotherapy and radiotherapy) are able to cure well-confined, primary tumors, the same does not apply during metastasis due to the systemic involvement and its resistance to conventional therapies. Therefore, the current clinical challenge is to develop new drugs and treatment modalities that will significantly impact the cure rates. In this sense, the present study aimed to evaluate the anticancer effect and study the underlying cell death mechanisms of diaryl diselenides and its substituted structures - (4-ClC6H4Se)2, (3-CF3C6H4Se)2 e (4-MeOC6H4Se)2 - on the human colon adenocarcinoma cell line (HT-29). We verified that (3-CF3C6H4Se)2 and (4-MeOC6H4Se)2 induced cytotoxicity through apoptosis mechanisms in HT-29 cells, where pro-apoptotic genes were up-regulated (Bax, caspase-9, caspase-8, apoptosis-inducing factor (AIF) and endonuclease G (EndoG), and anti-apoptotic genes were down-regulated (Bcl-2 and survivin). In a second moment we evaluated the anticancer potential of Canavalia brasiliensis (ConBr), Canavalia boliviana (ConBol) and Canavalia ensiformis (ConA) lectins in HT-29 cells, which showed an effective capacity to reduce cell viability. Once the anticancer effect was confirmed, lectins were labeled with FITC and its interaction with the tumor cells was investigated. The FITC-ConA and FITC-ConBol demonstrated the potential to bind to HT-29 cells unlike FITC-ConBr. In order to investigate a new treatment modality, the interaction between the respective lectins with HT-29 was evaluated when associated with functionalized multi-walled carbon nanotubes (f-MWCNTs). When f-MWNT was incorporated to FITC-ConBol and FITC-ConA lectins there was an increase in fluorescence intensity