We have demonstrated for the first time that the steroid metabolite, 2-methoxyestradiol (2-ME) is a powerful growth inhibitor of human osteosarcoma 143 B cell line by pleiotropic mechanisms involving cell cycle arrest at two different points and apoptosis. The ability of 2-ME to inhibit cell cycle at the respective points has been found concentration dependent. 1 microM 2-ME inhibited cell cycle at G1 phase while 10 microM 2-ME caused G2/M cell cycle arrest. As a natural estrogen metabolite 2-ME is expected to perturb the stability of microtubules (MT) in vivo analogously to Taxol--the MT binding anticancer agent. Contrary to 2-ME, Taxol induced accumulation of osteosarcoma cells in G2/M phase of cell cycle only. The presented data strongly suggest two different mechanisms of cytotoxic action of 2-ME at the level of a single cell.
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Postgrad Med J
January 2025
Proof of Concept Center, Eastern Hepatobiliary Surgery Hospital, Third Affiliated Hospital, Second Military Medical University, Naval Medical University, No. 255, Yangpu District, Shanghai, 200433, China.
Objectives: The objective was to investigate the role of double extraction in reducing data errors in evidence synthesis for pharmaceutical and non-pharmaceutical interventions.
Design: Crossover randomized controlled trial (RCT).
Setting: University and hospital with teaching programs in evidence-based medicine.
N4-acetylcytidine (ac4C) modification is a crucial RNA modification widely present in eukaryotic RNA. Previous studies have demonstrated that ac4C plays a pivotal role in viral infections. Despite numerous studies highlighting the strong correlation between ac4C modification and cancer progression, its detailed roles and molecular mechanisms in normal physiological processes and cancer progression remain incompletely understood.
View Article and Find Full Text PDFEXCLI J
November 2024
Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43B, 07100 Sassari, Italy.
The p53-MDM2 pathway plays a crucial role regulating tumor suppression and is a focal point of cancer research. This literature review delves into the complex interplay between the tumor suppressor protein p53 and its main regulator MDM2, highlighting their interaction and implications in cancer development and progression. The review compiles and summarizes the existing understanding of the biology and regulation of p53 and MDM2, emphasizing their roles in various cellular processes, including cell cycle regulation, DNA repair, apoptosis, and metabolism.
View Article and Find Full Text PDFGenetic studies on the protist, provide a glimpse into the unexpectedly rich world of intracellular patterning that unfolds within the ciliate cell cortex. Ciliate pattern studies provide a useful counterpoint to animal models of pattern formation in that the unicellular model draws attention away from fields of cells (or nuclei) as the principal players in the metazoan pattern paradigm, focusing instead on fields of ciliated basal bodies serving as sources of positional information. In this study, we identify , a Polo kinase of , that serves as an important factor driving global, circumferential pattern.
View Article and Find Full Text PDFCoordinated expression of replication-dependent (RD) histones genes occurs within the Histone Locus Body (HLB) during S phase, but the molecular steps in transcription that are cell cycle regulated are unknown. We report that RNA Pol II promotes HLB formation and is enriched in the HLB outside of S phase, including G1-arrested cells that do not transcribe RD histone genes. In contrast, the transcription elongation factor Spt6 is enriched in HLBs only during S phase.
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