Biochim Biophys Acta Mol Cell Res
January 2025
Resistance to chemotherapy drugs, which commonly occurs during the treatment of colorectal cancer (CRC), can lead to tumor recurrence and metastasis, so combinational treatment strategies according to the cancer cell type are urgently needed to overcome drug resistance and increase therapeutic efficiency. To this end, the tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a promising anticancer strategy. Some CRC cell lines such as SW620 have low sensitivity to TRAIL, so additional sensitizers are required to make the strategy effective.
View Article and Find Full Text PDFBackground: Although autophagy is an important mediator of metformin antitumor activity, the role of metformin in the crosstalk between autophagy and apoptosis remains unclear. The aim was to confirm the anticancer effect by inducing apoptosis by co-treatment with metformin and OSMI-1, an inhibitor of O-GlcNAcylation, in colon cancer cells.
Methods: Cell viability was measured by MTT in colon cancer cell lines HCT116 and SW620 cells.
Thioredoxin-like protein 1 (TXNL1), one of the thioredoxin superfamily known as redox-regulator, plays an essential in maintaining cell survival via various antioxidant and anti-apoptotic mechanisms. It is well known that relationship between ischemia and oxidative stress, however, the role of TXNL1 protein in ischemic damage has not been fully investigated. In the present study, we aimed to determine the protective role of TXNL1 against on ischemic injury in vitro and in vivo using cell permeable Tat-TXNL1 fusion protein.
View Article and Find Full Text PDFLevels of O-GlcNAc transferase (OGT) and hyper-O-GlcNAcylation expression levels are associated with cancer pathogenesis. This study aimed to find conditions that maximize the therapeutic effect of cancer and minimize tissue damage by combining an OGT inhibitor (OSMI-1) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). We found that OSMI-1 treatment in HCT116 human colon cancer cells has a potent synergistic effect on TRAIL-induced apoptosis signaling.
View Article and Find Full Text PDFProline rich Akt substrate (PRAS40) is a component of mammalian target of rapamycin complex 1 (mTORC1) and activated mTORC1 plays important roles for cellular survival in response to oxidative stress. However, the roles of PRAS40 in dopaminergic neuronal cell death have not yet been examined. Here, we examined the roles of Tat-PRAS40 in MPP- and MPTP-induced dopaminergic neuronal cell death.
View Article and Find Full Text PDFThe combination of chemotherapy with chemosensitizing agents is a common approach to enhance anticancer activity while reducing the dose-dependent adverse side effects of cancer treatment. Herein, we investigated doxorubicin (DOX) and O-GlcNAc transferase (OGT) inhibitor OSMI-1 combination treatment, which significantly enhanced apoptosis in hepatocellular carcinoma cells (HepG2) as a result of synergistic drug action in disparate stress signaling pathways. Treatment with a low dose of DOX or a suboptimal dose of OSMI-1 alone did not induce apoptotic cell death in HepG2 cells.
View Article and Find Full Text PDFThe cause of progression to non-alcoholic fatty liver disease (NAFLD) is not fully understood. In the present study, we aimed to investigate how curcumin, a natural phytopolyphenol pigment, ameliorates NAFLD. Initially, we demonstrated that curcumin dramatically suppresses fat accumulation and hepatic injury induced in methionine and choline-deficient (MCD) diet mice.
View Article and Find Full Text PDFThe precise mechanism of hepatic cirrhosis remains largely unclear. In particular, a potential regulatory mechanism by which protein kinase C-delta (PKCδ ) affects profibrogenic gene expression involved in hepatic cirrhosis has never been explored. In the present study, we investigated whether PKCδ activation is involved in liver inflammatory fibrosis in both lipopolysaccharide (LPS)-treated RAW 264.
View Article and Find Full Text PDFHuman pyridoxal 5'-phosphate phosphatase (PLPP), also known as a chronophin, is a phosphatase belonging to subfamily II of the HAD phosphatases, characterized by a large cap domain. As a member of the subfamily, its cap-open conformation is expected for substrate binding. We determined apo and PLP-bound PLPP/chronophin structures showing a cap-closed conformation.
View Article and Find Full Text PDFThe potent cytotoxicity of reactive oxygen species (ROS) can cause various diseases, however, it may also serve as a powerful chemotherapeutic strategy capable of killing cancer cells. Oxalomalate (OMA, α-hydroxy-β-oxalosuccinic acid), a tricarboxylic acid intermediate, is a well-known competitive inhibitor of two classes of NADP-dependent isocitrate dehydrogenase (IDH) isoenzymes, which serve as the major antioxidants and redox regulators in the mitochondria and cytosol. In this study, we investigated the therapeutic effects of OMA in melanoma and elucidated the associated underlying mechanisms of action using in vitro and in vivo models.
View Article and Find Full Text PDFEpigenetic modifier lysine demethylase 3a (Kdm3a) specifically demethylates mono‑ and di‑methylated ninth lysine of histone 3 and belongs to the Jumonji domain‑containing group of demethylases. Kdm3a serves roles during various biological and pathophysiological processes, including spermatogenesis and metabolism, determination of sex, androgen receptor‑mediated transcription and embryonic carcinoma cell differentiation. In the present study, physiological functions of Kdm3a were evaluated during embryogenesis of Xenopus laevis.
View Article and Find Full Text PDFBackground: Lysine-specific histone demethylase 5C (KDM5C) belongs to the jumonji family of demethylases and is specific for the di- and tri-demethylation of lysine 4 residues on histone 3 (H3K4 me2/3). KDM5C is expressed in the brain and skeletal muscles of humans and is associated with various biologically significant processes. KDM5C is known to be associated with X-linked mental retardation and is also involved in the development of cancer.
View Article and Find Full Text PDFParkinson's disease (PD), a neurodegenerative disorder, is characterized by a loss of dopaminergic neurons in the substantia nigra (SN) of the brain and it is well known that the pathogenesis of PD is related to a number of risk factors including oxidative stress. Antioxidant 1 (ATOX1) protein plays a crucial role in various diseases as an antioxidant and chaperone. In this study, we determined whether Tat-ATOX1 could protect against 1-methyl-4-phenylpyridinium ion (MPP)-induced SH-SY5Y cell death and in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced animal model of PD.
View Article and Find Full Text PDFAims: Peroxiredoxin5 (Prdx5), a thioredoxin peroxidase, is an antioxidant enzyme that is widely studied for its antioxidant properties and protective roles in neurological and cardiovascular disorders. This study is aimed at investigating the functional significance of Prdx5 in mitochondria and at analyzing its roles in ciliogenesis during the process of vertebrate development.
Results: We found that several Prdx genes were strongly expressed in multiciliated cells in developing Xenopus embryos, and their peroxidatic functions were crucial for normal cilia development.
Reprod Biol Endocrinol
August 2018
Background: Mounting evidence shows that ROS regulation by various antioxidants is essential for the expression of enzymes involved in steroidogenesis and maintenance of progesterone production by the corpus luteum (CL). However, the underlying mechanisms of peroxiredoxin 1 (PRDX1), an antioxidant enzyme, in luteal function for progesterone production in mice have not been reported. The aim of this study was to evaluate the functional link between PRDX1 and progesterone production in the CL of Prdx1 knockout (K/O) mice in the functional stage of CL.
View Article and Find Full Text PDFThe mechanisms underlying the progression to non-alcoholic steatohepatitis (NASH) remain to be elucidated. In the present study, we aimed to identify the proteins involved in the pathogenesis of liver tissue inflammation and to investigate the effects of silibinin, a natural polyphenolic flavonoid, on steatohepatitis. We performed comparative proteomic analysis using methionine and choline-deficient (MCD) diet-induced NASH model mice.
View Article and Find Full Text PDFCadmium (Cd) is toxic to living organisms because it causes the malfunction of essential proteins and induces oxidative stress. NADP-dependent cytosolic isocitrate dehydrogenase (IDH) provides reducing energy to counteract oxidative stress via oxidative decarboxylation of isocitrate. Intriguingly, the effects of Cd on the activity of IDH are both positive and negative, and to understand the molecular basis, we determined the crystal structure of NADP-dependent cytosolic IDH in the presence of Cd.
View Article and Find Full Text PDFIron is an essential element for neuronal as well as cellular functions. However, Iron overload has been known to cause neuronal toxicity through mitochondrial fission, dysregulation of Ca, endoplasmic reticulum (ER) stress, and reactive oxygen species (ROS) production. Nevertheless, the precise mechanisms of iron-induced oxidative stress and mitochondria- and ER-related iron toxicity in neuronal cells are not fully understood.
View Article and Find Full Text PDFCell actin cytoskeleton is primarily modulated by Rho family proteins. RhoA regulates several downstream targets, including Rho-associated protein kinase (ROCK), LIM-Kinase (LIMK), and cofilin. Pre-mRNA processing factor 4B (PRP4) modulates the actin cytoskeleton of cancer cells via RhoA activity inhibition.
View Article and Find Full Text PDFPeroxiredoxin1 (Prdx1) is an antioxidant enzyme belonging to the peroxiredoxin family of proteins. Prdx1 catalyzes the reduction of HO and alkyl hydroperoxide and plays an important role in different biological processes. Prdx1 also participates in various age-related diseases and cancers.
View Article and Find Full Text PDFAlthough doxorubicin (Dox)-induced oxidative stress is known to be associated with cytotoxicity, the precise mechanism remains unclear. Genotoxic stress not only generates free radicals, but also affects actin cytoskeleton stability. We showed that Dox-induced RhoA signaling stimulated actin cytoskeleton alterations, resulting in central stress fiber disruption at early time points and cell periphery cortical actin formation at a later stage, in HeLa cells.
View Article and Find Full Text PDFAlthough reactive oxygen species (ROS) work as second messengers at sublethal concentrations, higher levels of ROS can kill cancer cells. Since cellular ROS levels are determined by a balance between ROS generation and removal, the combination of ROS generators, and the depletion of reducing substances greatly enhance ROS levels. Emodin (1,3,8-trihydroxy-6-methyl anthraquinone), a natural anthraquinone derivative from the root and rhizome of numerous plants, is a ROS generator that induces apoptosis in cancer cells.
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