| Autor: |
Nishimura FG; Unidade de Biotecnologia, Universidade de Ribeirão Preto (UNAERP), Ribeirao Preto 14096-900, Brazil., Sampaio BB; Unidade de Biotecnologia, Universidade de Ribeirão Preto (UNAERP), Ribeirao Preto 14096-900, Brazil., Komoto TT; Unidade de Biotecnologia, Universidade de Ribeirão Preto (UNAERP), Ribeirao Preto 14096-900, Brazil., da Silva WJ; Unidade de Biotecnologia, Universidade de Ribeirão Preto (UNAERP), Ribeirao Preto 14096-900, Brazil., da Costa MMG; Unidade de Biotecnologia, Universidade de Ribeirão Preto (UNAERP), Ribeirao Preto 14096-900, Brazil., Haddad GI; Unidade de Biotecnologia, Universidade de Ribeirão Preto (UNAERP), Ribeirao Preto 14096-900, Brazil., Peronni KC; Instituto para Pesquisa do Cancêr (IPEC), Guarapuava 85051-060, Brazil., Evangelista AF; Sergio Arouca National School of Public Health, Oswaldo Cruz Foundation, Manguinhos, Rio de Janeiro 21040-900, Brazil., Hossain M; School of Sciences, Indiana University Kokomo, Kokomo, IN 46904, USA., Dimmock JR; College of Pharmacy and Nutrition, University of Saskatchewan (USask), Saskatoon, SK S7N 5A2, Canada., Bandy B; College of Pharmacy and Nutrition, University of Saskatchewan (USask), Saskatoon, SK S7N 5A2, Canada., Beleboni RO; Unidade de Biotecnologia, Universidade de Ribeirão Preto (UNAERP), Ribeirao Preto 14096-900, Brazil., Marins M; Unidade de Biotecnologia, Universidade de Ribeirão Preto (UNAERP), Ribeirao Preto 14096-900, Brazil., Fachin AL; Unidade de Biotecnologia, Universidade de Ribeirão Preto (UNAERP), Ribeirao Preto 14096-900, Brazil. |
| Abstrakt: |
Breast cancer stands out as one of the most prevalent malignancies worldwide, necessitating a nuanced understanding of its molecular underpinnings for effective treatment. Hormone receptors in breast cancer cells substantially influence treatment strategies, dictating therapeutic approaches in clinical settings, serving as a guide for drug development, and aiming to enhance treatment specificity and efficacy. Natural compounds, such as curcumin, offer a diverse array of chemical structures with promising therapeutic potential. Despite curcumin's benefits, challenges like poor solubility and rapid metabolism have spurred the exploration of analogs. Here, we evaluated the efficacy of the curcumin analog NC2603 to induce cell cycle arrest in MCF-7 breast cancer cells and explored its molecular mechanisms. Our findings reveal potent inhibition of cell viability (IC50 = 5.6 μM) and greater specificity than doxorubicin toward MCF-7 vs. non-cancer HaCaT cells. Transcriptome analysis identified 12,055 modulated genes, most notably upregulation of GADD45A and downregulation of ESR1 , implicating CDKN1A -mediated regulation of proliferation and cell cycle genes. We hypothesize that the curcumin analog by inducing GADD45A expression and repressing ESR1 , triggers the expression of CDKN1A , which in turn downregulates the expression of many important genes of proliferation and the cell cycle. These insights advance our understanding of curcumin analogs' therapeutic potential, highlighting not just their role in treatment, but also the molecular pathways involved in their activity toward breast cancer cells. |
