Selection of new molecules and treatment modalities to fight cancer

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.O câncer é uma das principais causas de morte no mundo, onde os índices devem aumentar 50% até 2020. Embora a ressecção cirúrgica e terapias adicionais (como a quimioterapias e radioterapias) sejam capazes de curar tumores primários bem delimitados, o mesmo não se aplica a metástase devido ao seu envolvimento sistêmico e a resistência a terapias convencionais. Portanto, atualmente o desfio clínico é desenvolver novas drogas e modalidades de tratamentos que irão impactar significativamente as taxas de cura do câncer. Neste sentido, o presente trabalho objetivou avaliar o efeito antineoplásico e investigar a rota de apoptose induzido pelo disseleneto de diarila e seus derivados substituídos - (4-ClC6H4Se)2, (3-CF3C6H4Se)2 e (4-MeOC6H4Se)2 - em células 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 pró-apoptoticos (Bax, caspase-9, caspase-8, fator indutor de apoptose (AIF) e endonuclease G (EndoG)) foram altamente expressos e os genes anti-apoptótico (Bcl-2 e survivin) mostraram uma redução na sua expressão. Em um segundo momento avaliamos o potencial antineoplásico das lectinas Canavalia brasiliensis (ConBr), Canavalia boliviana (ConBol) e Canavalia ensiformis (ConA) em células HT-29, as quais se mostraram efetivas em reduzir a viabilidade celular. Uma vez confirmado o efeito antineoplásico, as lectinas forma marcadas com FITC e a sua interação com as células tumorais foi investigado. As lectinas FITC-ConA e FITC-ConBol demonstraram potencial de se ligar as células HT-29 ao contrário da FITC-ConBr. A fim de investigar uma nova modalidade de tratamento foi avaliada a interação entre as respectivas lectinas com as células HT-29 quando associadas à nanotubos de carbonos funcionalizados de paredes múltiplas (f-MWCNTs). Quando os f-MWCNTs foram incorporados as lectinas FITC-ConA e FITC-ConBol houve um aumentaram na intensidade de fluorescência