Breast cancer represents a critical global health issue, accounting for a substantial portion of cancer-related deaths worldwide. Metastasis, the spread of cancer cells to distant organs, is the primary cause of approximately 90% of breast cancer-related fatalities. Despite advances in cancer treatment, conventional chemotherapeutic drugs often encounter resistance and demonstrate limited efficacy against metastasis. Natural products have emerged as promising sources for innovative cancer therapies, with curcumin being one such example. However, despite its therapeutic potential, curcumin exhibits several limitations. Analogous compounds possessing enhanced bioavailability, potency, or specificity offer a promising avenue for overcoming these challenges and demonstrate potent anti-tumor activities. Our study investigates the antimetastatic potential of the curcumin analog NC2603 in breast cancer cells, utilizing BT-20 cells known for their migratory properties. Cell viability assessments were performed using the MTT reduction method, while migration inhibition was evaluated through scratch and Transwell migration assays. Transcriptome analysis via next-generation sequencing was employed to elucidate gene modulation and compound mechanisms, with subsequent validation using RT-qPCR. The IC50 of NC2603 was determined to be 3.5 μM, indicating potent inhibition of cell viability, and it exhibited greater specificity for BT-20 cells compared with non-cancerous HaCaT cells, surpassing the efficacy of doxorubicin. Notably, NC2603 demonstrated superior inhibition of cell migration in both scratch and Transwell assays compared with curcumin. Transcriptome analysis identified 10,620 modulated genes. We validated the expression of six: EGR3, ATF3, EMP1, SOCS3, ZFP36, and GADD45B, due to their association with migration inhibition properties. We hypothesize that the curcumin analog induces EGR3 expression, which subsequently triggers the expression of ATF3, EMP1, SOCS3, ZFP36, and GADD45B. In summary, this study significantly advances our comprehension of the intricate molecular pathways involved in cancer metastasis, while also examining the mechanisms of analog NC2603 and underscoring its considerable potential as a promising candidate for adjuvant therapy.

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.

Introdução A síndrome de takotsubo (STT) é uma condição médica caracterizada por disfunção regional reversível do ventrículo esquerdo (VE) e/ou ventrículo direito. Essa síndrome é frequentemente desencadeada por situações de estresse agudo físico ou emocional. Apresenta características semelhantes a um evento de síndrome coronariana aguda (SCA), porém sem anormalidade coronariana evidenciada por exames como angiografia. Além disso, na admissão, os pacientes com STT também manifestam valores de fração de ejeção do ventrículo esquerdo (FEVE) substancialmente menores quando comparados com os [...] Introdução A síndrome de takotsubo (STT) é uma condição médica caracterizada por disfunção regional reversível do ventrículo esquerdo (VE) e/ou ventrículo direito. Essa síndrome é frequentemente desencadeada por situações de estresse agudo físico ou emocional. Apresenta características semelhantes a um evento de síndrome coronariana aguda (SCA), porém sem anormalidade coronariana evidenciada por exames como angiografia. Além disso, na admissão, os pacientes com STT também manifestam valores de fração de ejeção do ventrículo esquerdo (FEVE) substancialmente menores quando comparados com os

Introduction Takotsubo syndrome (TTS) is a medical condition characterized by reversible regional dysfunction of the left ventricle (LV) and/or right ventricle. TTS is often triggered by situations of acute physical or emotional stress. It presents characteristics similar to an acute coronary syndrome (ACS) event, but without coronary abnormality evidenced by exams such as angiography. Furthermore, upon admission, patients with TTS also manifest substantially lower left ventricular ejection fraction (LVEF) values, when compared to those with ACS. Nonetheless, even with these [...] Introduction Takotsubo syndrome (TTS) is a medical condition characterized by reversible regional dysfunction of the left ventricle (LV) and/or right ventricle. TTS is often triggered by situations of acute physical or emotional stress. It presents characteristics similar to an acute coronary syndrome (ACS) event, but without coronary abnormality evidenced by exams such as angiography. Furthermore, upon admission, patients with TTS also manifest substantially lower left ventricular ejection fraction (LVEF) values, when compared to those with ACS. Nonetheless, even with these