Expression of the multidrug resistance (MDR) transporter P-glycoprotein (P-gp) has been demonstrated to be regulated by hypoxia-inducible factor-1alpha (HIF-1alpha) and inhibited by intracellular reactive oxygen species (ROS). Herein, P-gp and HIF-1alpha expression were investigated in multicellular prostate tumor spheroids overexpressing the ROS-generating enzyme Nox-1 in comparison to the mother cell line DU-145. In Nox-1-overexpressing tumor spheroids (DU-145Nox1) generation of ROS as well as expression of Nox-1 was significantly increased as compared to DU-145 tumor spheroids. ROS generation was significantly inhibited in the presence of the NADPH-oxidase antagonists diphenylen-iodonium chloride (DPI) and 4-(2-aminoethyl)benzenesulfonyl fluoride (AEBSF). Albeit growth kinetic of DU-145Nox1 tumor spheroids was decreased as compared to DU-145 spheroids, elevated expression of Ki-67 was observed indicating increased cell cycle activity. In DU-145Nox1 tumor spheroids, expression of HIF-1alpha as well as P-gp was significantly decreased as compared to DU-145 spheroids, which resulted in an increased retention of the anticancer agent doxorubicin. Pretreatment with the free radical scavengers vitamin E and vitamin C increased the expression of P-gp as well as HIF-1alpha in Nox-1-overexpressing cells, whereas no effect of free radical scavengers was observed on mdr-1 mRNA expression. In summary, the data of the present study demonstrate that the development of P-gp-mediated MDR is abolished under conditions of elevated ROS levels, suggesting that the MDR phenotype can be circumvented by modest increase of intracellular ROS generation.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1016/j.febslet.2005.06.078 | DOI Listing |
Methods Cell Biol
January 2025
Department of Oncology-Pathology, Karolinska Institutet, Solna, Sweden. Electronic address:
In recent years, three-dimensional (3D) cultures of tumor cells has emerged as an important tool in cancer research. The significance of 3D cultures, such as tumor spheroids, lies in their ability to mimic the in vivo tumor microenvironment more precisely, offering a nuanced understanding of immune responses within the context of tumor progression. In fact, the infiltration of cytotoxic lymphocytes is key to determining patients' prognosis in several types of cancer and response to immunotherapy.
View Article and Find Full Text PDFPhysiol Rep
January 2025
Developmental Biology and Cancer Research and Teaching Department, University College London, Great Ormond Street Institute of Child Health, London, UK.
Polycystic kidney diseases (PKD) are genetic disorders which disrupt kidney architecture and function. Autosomal recessive PKD (ARPKD) is a rare form of PKD, caused by mutations in PKHD1, and clinically more severe than the more common autosomal dominant PKD (ADPKD). Prior studies have implicated Hedgehog (Hh) signaling in ADPKD, with increased levels of Hh components in experimental ADPKD and reduced cystogenesis following pharmacological Hh inhibition.
View Article and Find Full Text PDFBiotechnol Bioeng
January 2025
Bioprinting Laboratories Inc., Dallas, Texas, USA.
Recent advancements in three-dimensional (3D) cell culture technologies, such as cell spheroids, organoids, and 3D bioprinted tissue constructs, have significantly improved the physiological relevance of in vitro models. These models better mimic tissue structure and function, closely emulating in vivo characteristics and enhancing phenotypic analysis, critical for basic research and drug screening in personalized cancer therapy. Despite their potential, current 3D cell culture platforms face technical challenges, which include user-unfriendliness in long-term dynamic cell culture, incompatibility with rapid cell encapsulation in biomimetic hydrogels, and low throughput for compound screening.
View Article and Find Full Text PDFMol Oncol
January 2025
Institute of Biochemistry and Molecular Medicine, University of Bern, Bern, Switzerland.
Transient receptor potential melastatin-4 (TRPM4) ion channel expression is upregulated in prostate cancer (PCa), contributing to increased cell proliferation, migration, adhesion, epithelial-to-mesenchymal transition, cell cycle shift, and alterations of intracellular Ca signaling. GEO2R platform analysis of messenger RNA (mRNA) expression of ~ 6350 genes in normal and malignant prostate tissue samples from 15 PCa patients demonstrates that TRPM4 expression is upregulated sixfold and is among the most significantly upregulated genes in PCa. We find that absence of TRPM4 reduced PCa tumor spheroid size and decreased PCa tumor spheroid outgrowth.
View Article and Find Full Text PDFCancer Chemother Pharmacol
January 2025
Human Genetics Laboratory, Institute of Natural Sciences, Federal University of Alfenas (UNIFAL-MG), Alfenas, MG, 37130-001, Brazil.
Purpose: Histone deacetylase 6 (HDAC6) plays a critical role in tumorigenesis and tumor progression, contributing to proliferation, chemoresistance, and cell motility by regulating microtubule architecture. Despite its upregulation in melanoma tissues and cell lines, the specific biological roles of HDAC6 in melanoma are not well understood. This study aims to explore the functional effects and underlying mechanisms of WT161, a selective HDAC6 inhibitor, in melanoma cell lines.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!