HIF and lymphoma

PURPOSE: Chemoresistance is a major factor contributing to the failure of cancer treatment. The conventional chemotherapy agent 5-fluorouracil (5-FU) has been used for cancer treatment for decades. However, its use is limited in the treatment of hepatocellular carcinoma (HCC) due to acquired resistance. Nrf2 (NF-E2-related factor 2) is known to be associated with drug resistance across a wide range of cancer types. Also, since arsenic trioxide (As2 O3 ) showed antitumor effects on HCC, the purpose of this study was to determine whether As2 O3 and Nrf2-siRNA could inhibit HCC synergistically...

In recent years, studies have reported the role of stress-regulatory hormones, including epinephrine, in regulating the progression of a few cancers. However, the tumor-promoting action of epinephrine is not yet investigated in T cell malignancy, a rare and complicated neoplastic disorder. More so, very little is known regarding the implication of epinephrine in the glucose metabolic rewiring in tumor cells. The present investigation showed that epinephrine enhanced the proliferation of T lymphoma cells through up- and down-regulating the expression of PCNA, cyclin D, and p53, respectively...

The transcription factor hypoxia-inducible factor 1α (HIF-1α) is expressed in several cancers under intratumoral hypoxic stress that arises during pathogenic processes, resulting in malignant progression. We previously reported that hypoxic stimulation enhances the growth potential of canine lymphoma cells by activating the HIF-1α signaling pathway. In contrast, evofosfamide (Evo) releases a DNA-alkylating moiety within hypoxic tumor regions, suggesting that Evo could serve as a hypoxia-targeting drug in canine lymphoma...

Background: Ginseng possesses antitumor effects, and ginsenosides are considered to be one of its main active chemical components. Ginsenosides can further be hydrolyzed to generate secondary saponins, and 20( R )-panaxotriol is an important sapogenin of ginsenosides. We aimed to synthesize a new ginsengenin derivative from 20( R )-panaxotriol and investigate its antitumor activity in vivo and in vitro . Methods: Here, 20( R )-panaxotriol was selected as a precursor and was modified into its derivatives...

The transcription factor hypoxia-inducible factor 1α (HIF-1α) is activated in response to oxygen deficiency, and is expressed in several cancers under intratumoral hypoxic stress that arises during pathogenic processes. Hypoxic stimulation enhanced the growth potential of canine lymphoma cells by activating the HIF-1α signalling pathway in a previously reported study. The aim of this study was to establish a molecular design strategy for a novel hypoxia-targeting therapy for intestinal T-cell lymphoma (ITL) in dogs...

Mitochondrial dysfunction plays a crucial role in the pathological physiology of polycystic ovary syndrome (PCOS). Mitochondrial quality control system is vital to maintaining mitochondrial function, includes mitochondrial biosynthesis, dynamics and mitophagy. While mitophagy as a specific autophagy, plays an important role in the mitochondrial quality control system and is mediated by some signaling pathways to eliminate the excessive production of reactive oxygen species (ROS), such as hypoxia-inducible factor (HIF)-1α/B-cell lymphoma-2 adenovirus E1B 19 kDa interacting protein 3 (BNIP3)...

While the association of hypoxia has been established in various types of solid cancers, little is known about its presence and existence in diffuse large B-cell lymphoma (DLBCL). The purpose of the present study was to evaluate the expression of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor A (VEGF-A) in DLBCL and to analyze the association of these factors with several clinical and pathological characteristics. The immunohistochemical protein expression of HIF-1α and VEGF-A was investigated in 34 de novo DLBCL tumor samples from January 2017 to December 2017 from the Department of Hematology/Medical Oncology and Anatomical Pathology at Dr Kariadi Hospital (Semarang, Indonesia)...

Neoplastic cells overexpress glucose transporters (GLUT), particularly GLUT1 and GLUT3, to support altered metabolism. Hence, novel strategies are being explored to effectively inhibit GLUTs for a daunting interference of glucose uptake. Glutor, a piperazine-2-one derivative, is a newly reported pan-GLUT inhibitor with a promising antineoplastic potential. However, several aspects of the underlying mechanisms remain obscure. To understand this better, tumor cells of thymic origin designated as Dalton's lymphoma (DL) were treated with glutor and analyzed for survival and metabolism regulatory molecular events...

BACKGROUND: Pulmonary arterial hypertension (PAH) is associated with oxidative stress and affects the survival and homing of transplanted mesenchymal stem cells (MSCs) as well as cytokine secretion by the MSCs, thereby altering their therapeutic potential. In this study, we preconditioned the MSCs with prostaglandin E1 (PGE1) and performed in vitro and in vivo cell experiments to evaluate the therapeutic effects of MSCs in rats with PAH. METHODS: We studied the relationship between PGE1 and vascular endothelial growth factor (VEGF) secretion, B-cell lymphoma 2 (Bcl-2) expression, and C-X-C chemokine receptor 4 (CXCR4) expression in MSCs and MSC apoptosis as well as migration through the hypoxia-inducible factor (HIF) pathway in vitro...

Objective: Cervical cancer is a common cancer in women. The drug resistance of chemotherapeutic agents has always been an urgent problem to be solved in clinics. The purpose of this study was to determine the role of tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein gamma polypeptide (YWHAG) in cervical cancer and explore the effect of Curcuma on cervical cancer and its possible mechanism. Methods: YWHAG expression in cervical cancer was confirmed using The Cancer Genome Atlas (TCGA) database...

Cyclic nucleotide phosphodiesterase 5 (PDE5) has been recently identified to play a crucial role in the progression of many cancers. PDE5 promotes tumorigenesis by dysregulating various cellular processes such as proliferation, apoptosis, angiogenesis, and invasion and migration. Interestingly, multiple studies have reported the promising chemosensitizing potential of PDE5 inhibitor sildenafil in breast, colon, prostate, glioma, and lung cancers. However, to date, the chemosensitizing action of sildenafil is not evaluated in T cell lymphoma, a rare and challenging neoplastic disorder...

ETHNOPHARMACOLOGICAL RELEVANCE: Erzhi Pill (EZP) is a traditional Chinese prescription that has marked effects in treating type 2 diabetes mellitus and diabetic nephropathy. However, its underlying pharmacological mechanisms in the treatment of diabetic cardiomyopathy (DCM), remain to be elucidated. AIM OF THE STUDY: This study aimed to apply an integrative pharmacological strategy to systematically evaluate the pharmacological effects and molecular mechanisms of EZP, and provide a solid theoretical basis for the clinical application of EZP in the treatment of DCM...

BACKGROUND: Oxidative stress results in the production of excess reactive oxygen species (ROS) and triggers hippocampal neuronal damage as well as occupies a key role in the pathological mechanisms of neurodegenerative disorders such as Alzheimer's disease (AD). A recent study confirmed that magnesium had an inhibitory effect against oxidative stress-related malondialdehyde in vitro . However, whether Magnesium-L-threonate (MgT) is capable of suppressing oxidative stress damage in amyloid β (Aβ)25-35 -treated HT22 cells and the AD mouse model still remains to be investigated...

BACKGROUND: Hypoxia is a hallmark of the tumor microenvironment (TME) and in addition to altering metabolism in cancer cells, it transforms tumor-associated stromal cells. Within the tumor stromal cell compartment, tumor-associated macrophages (TAMs) provide potent pro-tumoral support. However, TAMs can also be harnessed to destroy tumor cells by monoclonal antibody (mAb) immunotherapy, through antibody dependent cellular phagocytosis (ADCP). This is mediated via antibody-binding activating Fc gamma receptors (FcγR) and impaired by the single inhibitory FcγR, FcγRIIb...

Over-expressions of epidermal growth factor receptor and vascular endothelial growth factor receptor were frequently associated with the metastasis of solid tumors. Vandetanib, a dual tyrosine kinase inhibitor of epidermal growth factor receptor and vascular endothelial growth factor receptor, was broadly effective in treating a variety of human solid tumors. The compelling evidence that hypoxia is involved in tumor resistance to cancer therapy. Hypoxia-inducible factor (HIF-1α), a major transcription factor in response to hypoxia, has been considered as a promising specific target for cancer therapy...

BACKGROUND: The leaves of the plant Ilex latifolia Thunb. can be made into Kuding tea, which is a drink rich in polyphenols. This study aimed to observe the effect of Ilex latifolia Thunb. polyphenols (ILTPs) on human lung cancer cell line A549 (A549 cells) by regulating the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway. METHODS: In vitro cultured cells were treated with ILTPs; the proliferation of A549 cells and BEAS-2B human normal lung epithelial cells (Beas-2B cells) was observed using the 3-(4,5-dimethylazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and the survival status of A549 cells was observed by fluorescence staining...

Latency is a hallmark of herpesviruses, allowing them to persist into their host without virions production. Acute exposure to hypoxia (below 3% O2 ) was identified as a trigger of latent-to-lytic switch (reactivation) for human oncogenic gamma-herpesviruses (KSHV and EBV). Therefore, we hypothesized that hypoxia could also induce reactivation of Marek's disease virus (MDV), sharing biological properties with EBV and KSHV (notably oncogenic properties), into lymphocytes. Acute exposure to hypoxia (1% O2 ) of two MDV-latently infected cell lines derived from MD tumors (3867K and MSB-1) induced MDV reactivation...

Melanoma cells exploit mitophagy and hypoxia signaling to promote their growth. In a recent study, we found that loss of B-cell lymphoma 2 (BCL-2)/adenovirus E1B 19kDa protein-interacting protein 3 (BNIP3) curbed Hypoxia Inducible Factor 1 alpha (HIF-1α) levels and melanoma growth in vivo . Insufficient levels of BNIP3 boost iron-driven prolyl hydroxylase 2 (Phd2)-mediated degradation of HIF-1α by exacerbating nuclear receptor activator 4 (Ncoa4)-mediated ferritinophagy. Thus, BNIP3 promotes melanoma growth by controlling iron metabolism...

Targeting the first protein complex of the mitochondrial electron transport chain (MC1) in cancer has become an attractive therapeutic approach in the recent years, given the metabolic vulnerabilities of cancer cells. The anticancer effect exerted by the pleiotropic drug metformin and the associated reduction in hypoxia-inducible factor 1α (HIF-1α) levels putatively mediated by MC1 inhibition led to the development of HIF-1α inhibitors, such as BAY87-2243, with a more specific MC1 targeting. However, the development of BAY87-2243 was stopped early in phase 1 due to dose-independent emesis and thus there is still no clinical proof of concept for the approach...

BACKGROUND: Physciosporin (PHY) is one of the potent anticancer lichen compound. Recently, PHY was shown to suppress colorectal cancer cell proliferation, motility, and tumorigenesis through novel mechanisms of action. PURPOSE: We investigated the effects of PHY on energy metabolism and tumorigenicity of the human breast cancer (BC) cells MCF-7 (estrogen and progesterone positive BC) and MDA-MB-231 (triple negative BC). METHODS: The anticancer effect of PHY on cell viability, motility, cancer metabolism and tumorigenicity was evaluated by MTT assay, migration assay, clonogenic assay, anchorage-independent colony formation assay, glycolytic and mitochondrial metabolism analysis, qRT-PCR, flow cytometric analysis, Western blotting, immunohistochemistry in vitro; and by tumorigenicity study with orthotopic breast cancer xenograft model in vivo...