• BMB Reports
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• v.51 no.11
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• pp.557-562
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• 2018

Reactive oxygen species (ROS) are major sources of cellular oxidative stress. Specifically, cancer cells harbor genetic alterations that promote a continuous and elevated production of ROS. While such oxidative stress conditions could be harmful to normal cells, they facilitate cancer cell growth in multiple ways by causing DNA damage and genomic instability, and ultimately by reprogramming cancer cell metabolism. This review provides up to date findings regarding the roles of ROS generation induced by diverse biological molecules and chemicals in representative women's cancer. Specifically, we describe the cellular signaling pathways that regulate direct or indirect interactions between ROS homeostasis and metabolism within female genital cancer cells.

• Biomolecules & Therapeutics
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• v.31 no.3
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• pp.264-275
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• 2023

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by tremors, bradykinesia, and rigidity. PD is caused by loss of dopaminergic (DA) neurons in the midbrain substantia nigra (SN) and therefore, replenishment of DA neurons via stem cell-based therapy is a potential treatment option. Astrocytes are the most abundant non-neuronal cells in the central nervous system and are promising candidates for reprogramming into neuronal cells because they share a common origin with neurons. The ability of neural progenitor cells (NPCs) to proliferate and differentiate may overcome the limitations of the reduced viability and function of transplanted cells after cell replacement therapy. Achaete-scute complex homolog-like 1 (Ascl1) is a well-known neuronal-specific factor that induces various cell types such as human and mouse astrocytes and fibroblasts to differentiate into neurons. Nurr1 is involved in the differentiation and maintenance of DA neurons, and decreased Nurr1 expression is known to be a major risk factor for PD. Previous studies have shown that direct conversion of astrocytes into DA neurons and NPCs can be induced by overexpression of Ascl1 and Nurr1 and additional transcription factors genes such as superoxide dismutase 1 and SRY-box 2. Here, we demonstrate that astrocytes isolated from the ventral midbrain, the origin of SN DA neurons, can be effectively converted into DA neurons and NPCs with enhanced viability. In addition, when these NPCs are inducted to differentiate, they exhibit key characteristics of DA neurons. Thus, direct conversion of midbrain astrocytes is a possible cell therapy strategy to treat neurodegenerative diseases.

• Reproductive and Developmental Biology
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• v.35 no.3
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• pp.301-306
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• 2011

Fibroblasts of large animals are easy to isolate and to maintain in vitro culture. Thus, these cells are extensively applied to donor cell for somatic cell nuclear transfer, and to substrate cells to generate induced pluripotent stem cells after transfection of requited genes to be essentially required for direct reprogramming. However, limited mitotic activity of fibroblasts to differentiate along a terminal lineage becomes restrictive for their versatile application. Recently, commercial culture medium and systems developed for primary cells are provided by manufactures. In this study, we examined whether one of the systems developed for primary fibroblasts of human are effective on porcine ear skin fibroblasts. To this end, we performed proliferation assay after five days culture in vitro of porcine fibroblasts in medium DMEM, which is generally used for fibroblasts culture, and medium M106 for human dermal fibroblasts, supplemented with various concentrations of FBS and LSGS contained mainly growth factors, respectively. Consequence was that presence of 15% FBS and 0.1 ${\times}$ concentrations of LSGS in DMEM showed most active proliferation of porcine fibroblasts.

• Molecules and Cells
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• v.45 no.4
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• pp.202-215
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• 2022

The androgen receptor (AR) is an important therapeutic target for treating prostate cancer (PCa). Moreover, there is an increasing need for understanding the AR-independent progression of tumor cells such as neuroendocrine prostate cancer (NEPC). Menin, which is encoded by multiple endocrine neoplasia type 1 (MEN1), serves as a direct link between AR and the mixed-lineage leukemia (MLL) complex in PCa development by activating AR target genes through histone H3 lysine 4 methylation. Although menin is a critical component of AR signaling, its tumorigenic role in AR-independent PCa cells remains unknown. Here, we compared the role of menin in AR-positive and AR-negative PCa cells via RNAi-mediated or pharmacological inhibition of menin. We demonstrated that menin was involved in tumor cell growth and metastasis in PCa cells with low or deficient levels of AR. The inhibition of menin significantly diminished the growth of PCa cells and induced apoptosis, regardless of the presence of AR. Additionally, transcriptome analysis showed that the expression of many metastasis-associated genes was perturbed by menin inhibition in AR-negative DU145 cells. Furthermore, wound-healing assay results showed that menin promoted cell migration in AR-independent cellular contexts. Overall, these findings suggest a critical function of menin in tumorigenesis and provide a rationale for drug development against menin toward targeting high-risk metastatic PCa, especially those independent of AR.