Trans-chalcone increases p53 activity via DNAJB1/HSP40 induction and CRM1 inhibition

Autor(es):Mostrar menos -

Silva, Gabriel ^[1] ; Marins, Mozart ^{[1, 2]} ; Chaichanasak, Nadda ^[3] ; Yoon, Yongdae ^[3] ; Fachin, Ana Lucia ^{[1, 2]} ; Pinhanelli, Vitor Caressato ^[1] ; Regasini, Luis Octavio ^[4] ; dos Santos, Mariana Bastos ^[4] ; Ayusso, Gabriela Miranda ^[4] ; Marques, Beatriz de Carvalho ^[4] ; Wu, Wells W. ^[5] ; Phue, Je-Nie ^[5] ; Shen, Rong-Fong ^[5] ; Baek, Seung Joon ^[3]

Afiliação do(s) autor(es)

^[1] Univ Ribeirao Preto, Biotechnol Unit, Ribeirao Preto, SP - Brazil

^[2] Univ Ribeirao Preto, Med Sch, Ribeirao Preto, SP - Brazil

^[3] Seoul Natl Univ, Coll Vet Med & Res Inst Vet Sci, Lab Signal Transduct, Seoul - South Korea

^[4] Sao Paulo State Univ UNESP, Dept Chem & Environm Chem, Sao Paulo - Brazil

^[5] US FDA, Facil Biotechnol Resources, CBER, Silver Spring, MD - USA

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 13, n. 8 AUG 17 2018.
• Citações Web of Science: 3

Resumo

Naturally-occurring chalcones and synthetic chalcone analogues have been demonstrated to have many biological effects, including anti-inflammatory, anti-malarial, anti-fungal, and anti-oxidant/anti-cancerous activities. Compared to other chalcones, trans-chalcone exhibits superior inhibitory activity in cancer cell growth as shown via in vitro assays, and exerts anti-cancerous effects via the activation of the p53 tumor suppressor protein. Thus, characterization of the specific mechanisms, by which trans-chalcone activates p53, can aid development of new chemotherapeutic drugs that can be used individually or synergistically with other drugs. In this report, we found that trans-chalcone modulates many p53 target genes, HSP40 being the most induced gene in the RNA-Seq data using trans-chalcone-treated cells. CRM1 is also inhibited by trans-chalcone, resulting in the accumulation of p53 and other tumor suppressor proteins in the nucleus. Similar effects were seen using trans-chalcone derivatives. Overall, trans-chalcone could provide a strong foundation for the development of chalcone-based anti-cancer drugs. (AU)

• Processo FAPESP: 14/15307-7 - Análise molecular da resposta de linhagens tumorais humanas e caninas ao flavonóide trans-chalcona
• Beneficiário: Mozart de Azevedo Marins
• Modalidade de apoio: Auxílio à Pesquisa - Regular