Disease relevance of shikonin

• Additionally, shikonin inhibited the replication of a multidrug-resistant strain and pediatric clinical isolates of HIV in human peripheral blood mononuclear cells, with 50% inhibitory concentrations (IC(50)s) ranging from 96 to 366 nM [1].
• In this study, we assessed the effects of shikonin on chemokine receptor function and HIV-1 replication [1].
• Involvement of reactive oxygen species, but not mitochondrial permeability transition in the apoptotic induction of human SK-Hep-1 hepatoma cells by shikonin [2].
• Beta-hydroxyisovalerylshikonin (beta-HIVS), a compound isolated from Lithospermium radix, most efficiently induced cell-death in two lines of lung cancer cells, namely, NCI-H522 and DMS114, whereas shikonin was effective against a wide variety of tumor cell lines [3].
• Shikonin modulates cell proliferation by inhibiting epidermal growth factor receptor signaling in human epidermoid carcinoma cells [4].

High impact information on shikonin

• We demonstrated that shikonin-inhibitory response was retained in the core TNF-alpha promoter region containing the TATA box and a 48-bp downstream sequence relative to the transcription start site [5].
• Further our results indicated that shikonin suppressed the basal transcription and activator-regulated transcription of TNF-alpha by inhibiting the binding of transcription factor IID protein complex (TATA box-binding protein) to TATA box [5].
• Shikonin inhibited the phosphatidylinositol 3,4,5-triphosphate (PtdIns-3,4,5-P3) phosphatase activity of recombinant phosphatase and tensin homolog deleted on chromosome 10 (PTEN) with an IC50 value of 2.7 microM [6].
• A naphthoquinone derivative, shikonin, has insulin-like actions by inhibiting both phosphatase and tensin homolog deleted on chromosome 10 and tyrosine phosphatases [6].
• Its effect on tyrosine phosphorylation in intact cells was far weaker than that of pervanadate, a widely used tyrosine phosphatase inhibitor, despite the observation that the effect of shikonin on PKB was more potent than that of pervanadate [6].

Biological context of shikonin

• In this study, we evaluated the effects of shikonin and its derivatives on the transcriptional activation of human TNF-alpha promoter in a gene gun-transfected mouse skin system by using a luciferase reporter gene assay [5].
• The 1,4-naphthoquinone derivative, shikonin, has been shown to increase glucose uptake by adipocytes and myocytes with minor effects on protein tyrosine phosphorylation in the cells (Biochem Biophys Res Commun 292:642-651, 2002) [6].
• Shikonin is a major component of zicao (purple gromwell, the dried root of Lithospermum erythrorhizon), a Chinese herbal medicine with various biological activities, including inhibition of human immunodeficiency virus (HIV) type 1 (HIV-1) [1].
• A selective acylation at 1'-OH of shikonin in the presence of dicyclohexylcarbodiimide and 4-(dimethylamino)pyridine gave rise to a good yield of corresponding acylshikonin derivatives [7].
• White light, which inhibits shikonin formation, was shown to strongly suppress HMGR gene expression [8].

Anatomical context of shikonin

• In addition to its effect on PTEN, shikonin was found to inhibit several protein phosphatases in cell-free systems [6].
• Shikonin also effectively inhibited the replication of the HIV Ba-L isolate in monocytes/macrophages, with an IC(50) of 470 nM [1].
• In this report, we showed that the administration of shikonin could result in the induction of apoptotic cell death of human hepatoma cell line, SK-Hep-1 [2].
• The shikonin pigments were also stored on the cell walls as oil droplets [9].
• Impairment of vascular function of rat thoracic aorta in an endothelium-dependent manner by shikonin/alkannin and derivatives isolated from roots of Macrotomia euchroma [10].

Associations of shikonin with other chemical compounds

• Lithospermum erythrorhizon produces red naphthoquinone pigments that are shikonin derivatives [11].
• Geranylhydroquinone 3"-hydroxylase, which is likely to be involved in shikonin and dihydroechinofuran biosynthesis, was identified in cell suspension cultures of Lithospermum erythrorhizon Sieb. et Zucc [12].
• The requirement of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR, EC 1.1.1.34), a key enzyme of the mevalonate route to isoprenoids, for shikonin synthesis was investigated [8].
• The potency of inhibiting collagen-induced platelet aggregation is in the following order: acetylshikonin (IC50 = 2.1 microM), teracrylshikonin (2.8 microM), beta, beta-dimethylacrylshikonin (4.2 microM), and shikonin (10.7 microM) [13].
• Besides shikonin and arnebifuranone, two new shikonin esters isolated from the roots of Arnebia hispidissima have been characterized as butylshikonin and 2'-methyl-hexa-1',3'-dienoylshikonin by physicochemical methods [14].

Gene context of shikonin

• BACKGROUND: The role of extracellular signal-regulated kinase 1/2 (ERK1/2) in shikonin-induced HeLa cells apoptosis remains vague [15].
• However, shikonin inhibited neither RANTES nor MIP-1alpha binding to CCR5 transfected HEK/293 cells [16].
• Additionally, shikonin blocked RANTES and MIP-1alpha binding to stable CC chemokine receptor-1 (CCR1) transfected human embryonic kidney (HEK)/293 cells with IC50 values of 2.63 x 10(-6) and 2.57 x 10(-6) M, respectively [16].
• The inhibition by beta-HIVS of the activities of EGFR and v-Src was much stronger than that by shikonin [3].
• Human ACAT inhibitory effects of shikonin derivatives from Lithospermum erythrorhizon [17].

Analytical, diagnostic and therapeutic context of shikonin

• Geranyldiphosphate:4-hydroxybenzoate 3-geranyltransferase is a regulatory enzyme in the biosynthesis of shikonin, a phytoalexin and pharmaceutical produced by cell cultures of Lithospermum erythrorhizon Sieb. et Zucc [18].
• Genetic engineering of shikonin biosynthesis hairy root cultures of Lithospermum erythrorhizon transformed with the bacterial ubiC gene [19].
• Molecular cloning and characterization of a cDNA encoding a novel apoplastic protein preferentially expressed in a shikonin-producing callus strain of Lithospermum erythrorhizon [9].
• Shikonin induced DNA fragmentation into the multiples of 180 bp and increased the percentage of hypodiploid cells in flow cytometry after propidium iodide staining [20].
• The derivatives 3-9 showed stronger anti-MRSA activity [minimum inhibitory concentrations (MICs) ranged from 1.56 to 3.13 microg/mL] than alkannin or shikonin (MIC = 6.25 microg/mL) [21].

References