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Shikonin‑mediated inhibition of nestin affects hypoxia‑induced proliferation of pulmonary artery smooth muscle cells.
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The imbalance between the proliferation and apoptosis of pulmonary artery smooth muscle cells (PASMCs) is of importance in pulmonary vascular remodeling. Shikonin, a naphthoquinone compound extracted from the Chinese medicinal herb Lithospermum erythrorhizon, inhibits the proliferation of rat smooth
Shikonin suppresses proliferation and induces cell cycle arrest through the inhibition of hypoxia-inducible factor-1α signaling.
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Hypoxia enhances the development of solid tumors. Hypoxia-inducible factor-1α (HIF-1α) is a transcription factor that is dominantly expressed under hypoxia in solid tumor cells and is a key factor of tumor regulation. HIF-1α regulates several target genes involved in many aspects of cancer
Shikonin protects H9C2 cardiomyocytes against hypoxia/reoxygenation injury through activation of PI3K/Akt signaling pathway.
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Myocardial ischemic/reperfusion (I/R) injury often leads to irreversible myocardial cell death and even heart failure, with limited therapeutic possibilities. In the present study, we evaluated the protective effects of shikonin (SHK) against hypoxia/reoxygenation (H/R)-induced cardiomyocyte damage
Cancer therapeutic agents targeting hypoxia-inducible factor-1.
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The discovery of hypoxia-inducible factor-1 has led to a rapidly increasing understanding of the molecular mechanism of tumor hypoxia in the past two decades. Today it is generally accepted that HIF-1 plays a pivotal role in the cellular response to tumor hypoxia which represents a major obstacle to
Synthesis and biological activity of novel shikonin analogues.
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A series of shikonin analogues with side chain variants have been synthesized and evaluated for antitumor activity. These novel analogues show a broad spectrum of in vitro cytotoxicity against various cancer cell lines. Additionally, some analogues were also found to have the ability to decrease the
Shikonin Suppresses Lymphangiogenesis via NF-κB/HIF-1α Axis Inhibition.
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Lymphangiogenesis, the formation of lymphatic vessels from preexisting ones, promotes cancer growth and metastasis. Finding natural compounds with anti-lymphangiogenic activity will be useful for preventive treatment of lymphatic metastasis. Shikonin, an ingredient of a traditional Japanese and
Anti-inflammatory properties of shikonin contribute to improved early-stage diabetic retinopathy.
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Diabetic retinopathy (DR), a major microvascular complication of diabetes, leads to retinal vascular leakage, neuronal dysfunction, and apoptosis within the retina. In this study, we combined STZ with whole-body hypoxia (10% O2) for quicker induction of early-stage retinopathy in C57BL/6 mice. We
Efficacy of Shikonin against Esophageal Cancer Cells and its possible mechanisms in vitro and in vivo.
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Increasing evidences indicate that shikonin can suppress the tumor growth. However, the mechanisms remain elusive. In the present study, we investigated the effects and mechanisms of shikonin against esophageal cancer. The expression of hypoxia inducible factor 1α (HIF1α) and pyruvate kinase M2
Ferroxitosis: a cell death from modulation of oxidative phosphorylation and PKM2-dependent glycolysis in melanoma.
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Reliance on glycolysis is a characteristic of malignancy, yet the development of resistance to BRAF inhibitors in melanoma is associated with gain of mitochondrial function. Concurrent attenuation of oxidative phosphorylation and HIF-1α/PKM2-dependent glycolysis promotes a non-apoptotic, iron- and
Glycolysis inhibitors suppress renal interstitial fibrosis via divergent effects on fibroblasts and tubular cells.
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Renal interstitial fibrosis is a common pathological feature of chronic kidney disease that may involve changes of metabolism in kidney cells. In the present study, we first showed that blockade of glycolysis with either dichloroacetate (DCA) or shikonin to target different glycolytic enzymes
Pyruvate Kinase Isozymes M2 and Glutaminase Might Be Promising Molecular Targets for the Treatment of Gastric Cancer.
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The aim of this study was to analyze the significance of glucose metabolism-related enzymes in the proliferation of gastric cancer under hypoxia. Four hypoxia-resistant gastric cancer cell lines and four parent cell lines were used. Reverse transcription-PCR was used to evaluate the mRNA expression
Xue-fu-Zhu-Yu decoction protects rats against retinal ischemia by downregulation of HIF-1α and VEGF via inhibition of RBP2 and PKM2.
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BACKGROUND
Retinal ischemia-related eye diseases result in visual dysfunction. This study investigates the protective effects and mechanisms of Xue-Fu-Zhu-Yu decoction (XFZYD) with respect to retinal ischemia.
METHODS
Retinal ischemia (I) was induced in Wistar rats by a high intraocular pressure
Role of pyruvate kinase m2 in oxidized LDL induced macrophage foam cell formation and inflammation.
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Pyruvate kinase M2 (PKM2) links metabolic and inflammatory dysfunction in atherosclerotic coronary artery disease; however, its role in Ox-LDL induced macrophage foam cell formation, and inflammation is unknown and therefore presently studied. In rGM-CSF differentiated murine bone marrow-derived
Lapachol inhibits glycolysis in cancer cells by targeting pyruvate kinase M2.
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Reliance on aerobic glycolysis is one of the hallmarks of cancer. Although pyruvate kinase M2 (PKM2) is a key mediator of glycolysis in cancer cells, lack of selective agents that target PKM2 remains a challenge in exploiting metabolic pathways for cancer therapy. We report that unlike its
PKM2 inhibition may reverse therapeutic resistance to transarterial chemoembolization in hepatocellular carcinoma
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Background: Therapeutic options for patients with hepatocellular carcinoma (HCC) are limited. Transarterial chemoembolization (TACE) is an interventional procedure used to deliver chemotherapy and embolizing agents directly to the tumor and is the procedure of
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