Biology subjects

Zuniga-Eulogio, M. D.

Publications and source records attributed to Zuniga-Eulogio, M. D..

3 recordsLinked to original sources

bioRxiv2023

The isoflavonoid brazilin inhibits viability and cell migration in breast cancer cells

Breast cancer is the most common neoplasm diagnosed in women and is the leading cause of cancer death worldwide. In recent years, compounds isolated from natural sources have been proposed as potential molecules in therapy for breast cancer. In this regard, brazilin has been evaluated in various biological sceneries and has shown pharmacological functions, including anticancer and anti-inflammatory activities. Brazilin was obtained from Haematoxylum brasiletto. The chemical structure was confirmed by spectroscopic data (1H-NMR, 13C-NMR). Concerning biological activity, by MTT assays, brazilin showed cytotoxic effects on MCF7 and MDA-MB-231 breast cancer cell lines. Interestingly, brazilin was not toxic in MCF10A non-tumorigenic breast epithelial cells. We also observed morphological changes to a rounded phenotype associated with apoptosis in breast cancer cell lines and decreased cell migration in a dose and time-dependent manner. By in silico analysis, we found that brazilin interacts with JAK1, JAK2, and iNOS, essential molecules driven cell migration and metastasis in cancer. These data suggest that brazilin can potentially be used as an anti-cancer agent in the future.

cancer biology↗

bioRxiv2023

Differential requirements for different subfamilies of the mammalian SWI/SNF chromatin remodeling enzymes in myoblast differentiation

Mammalian SWI/SNF (mSWI/SNF) complexes are ATP-dependent chromatin remodeling enzymes that are critical for normal cellular functions and that are mis-regulated in [~]20% of human cancers. These enzymes exhibit significant diversity in the composition of individual enzyme complexes. mSWI/SNF enzymes are classified into three general sub-families based on the presence or absence of specific subunit proteins. The three sub-families are called BAF (BRM or BRG1-associated factors), ncBAF (non-canonical BAF), and PBAF (Polybromo-associated BAF). The biological roles for the different subfamilies of mSWI/SNF enzymes are poorly described. We knocked down (KD) the expression of genes encoding subunit proteins unique to each of the three subfamilies, Baf250A, Brd9, and Baf180, which mark the BAF, ncBAF, and PBAF sub-families, respectively, and examined the requirement for each in myoblast differentiation. We found that BAF250A and the BAF complex was required to drive lineage-specific gene expression during myoblast differentiation. KD of Baf250A reduced the expression of the lineage determinant Myogenin and other differentiation markers, due to decreased binding of BAF250A to myogenic gene promoters. KD of Brd9 delayed myoblast differentiation. However, RNA-seq analysis revealed that while the Baf250A-dependent gene expression profile included genes involved in myogenesis, the Brd9-dependent gene expression profile did not. Moreover, no-colocalization of Baf250A and Brd9 was observed in differentiating cells, suggesting independent mechanisms of action for BAF and ncBAF complexes in myogenesis. The PBAF complex was dispensable for myoblast differentiation. The results distinguish between the roles of the mSWI/SNF enzyme subfamilies during myoblast differentiation.

molecular biology↗

bioRxiv2019

Leptin induces cell migration and invasion in a FAK-Src- dependent manner in breast cancer cells

Breast cancer is the most common invasive neoplasia, and the second leading cause of death associated with cancer in women worldwide. Mammary tumorigenesis is severely linked to obesity, the potential connection is leptin. Leptin is a hormone secreted by adipocytes, which contributes to the progression of breast cancer. Cell migration, metalloproteases secretion, and invasion are cellular processes associated with various stages of metastasis. These processes are regulated by the kinases FAK and Src. In this study, we utilized the breast cancer cell lines MCF7 and MDA-MB-231 to determine the effect of leptin on FAK and Src kinases activation, cell migration, metalloproteases secretion, and invasion. By Western blot we found that leptin activates FAK and Src, and induces the localization of FAK to the focal adhesions. Specific inhibitors of FAK and Src showed that the effect exerted by leptin in cell migration, and invasion in breast cancer cells is dependent on these kinases. Moreover, by gelatin zymmography we established that leptin promotes the secretion of the extracellular matrix remodelers, MMP-2 and MMP-9, in a FAK and Src dependent manner. Our findings strongly suggest that leptin promotes the development of a more aggressive invasive phenotype in mammary cancer cells.

cell biology↗