Induction of apoptosis by shikonin through a rosjnk. Nov 30, 2017 plants are a rich source of valuable chemicals that are used as herbal and modern medicines. Shikonin s production and use as a mordant dye for fabrics and cosmetics may result in its release to the environment through various waste streams. Pdf search engine allows you to find free pdf books and files and download them to your computer. Aug 12, 2002 alkannin and shikonin, two natural products from alkanna tinctoria and lithospermum erhythrorhizon boraginaceae, are used in folk medicine where they are claimed to possess, among other properties, wound healing and anti. Notably, nac dramatically decreased shikonin induced ros production in both k1 and ftc3 cells figure 3a and supplemental figure 2. To fulfill this, a549 lung cancer cells were treated with shikonin and then subjected to. Synthesis, biological function and evaluation of shikonin. Research paper efficacy of shikonin against esophageal cancer. Here, our results demonstrate that shikonin is able to sensitize human breast cancer cells to chemotherapy by paclitaxel taxol. Research paper efficacy of shikonin against esophageal. Traditional chinese medicine tcm is a healing art that has been practiced for thousands of years.
Due to increased drug resistance and the severe side effects of currently used therapeutics, new candidate compounds are required for improvement of therapy success. Shikonin exhibits significant cytotoxic activity against multiple cancer cell types in vitro and in vivo 2,3, and a number of studies have previously established a potential role for shikonin as a. Optimization of shikonin homogenate extraction from. It is also an inhibitor of tmem16a chloride channel activity using cellbased fluorescent.
Here we report that shikonin inhibited the growth of a wide range of human cancer cell lines, illustrating a broad anticancer effect. This may be one of the mechanisms of action that gives shikonin its antiinflammatory properties. Recent studies have shed light on the molecular mechanisms underlying these biological activities of shikonin. Sensitizing the therapeutic efficacy of taxol with. Despite being among the longeststudied plant natural products, there are still many gaps in knowledge about shikoninalkannin pathway genes. Us20050222258a1 us11129,255 us12925505a us2005222258a1 us 20050222258 a1 us20050222258 a1 us 20050222258a1 us 12925505 a us12925505 a us 12925505a us 2005222258 a1 us2005222258 a1 us 2005222258a1 authority us united states prior art keywords medicament stated shikonin virus compounds prior art date 20030221 legal status the legal status is an. Enhanced shikonin production from lithospermum erythrorhizon by. The root cells in the bioreactor create 23% shikonin in only 23 days. The aqueous solution was acidified, and free shikonin was recovered by. Shikonin, a naphthoquinone compound, rapidly induces cell death of human myeloma cells via production of reactive oxygen species takahiro kimura1, tomonori nakazato 1,2 and masahiro kizaki3 shikonin is a naphthoquinone derivative extracted from a traditional chinese medical herb, lithospermum erythrorhizon. Used as an antiinflammatory treatment in traditional chinese medicine tcm.
The results of experiments indicated that parahydroxybenzoic acid 20 was. Lithospermum erythrorhizon bmc plant biology biomed central. The chemistry and biology of alkannin, shikonin, and related naphthazarin natural products. Shikonin is a naturally occurring naphthoquinone derivative that displays antiinflammatory and antitumor properties. Shikonin is a natural naphthoquinone compound and has demonstrated potent anticancer activities. Pdf biotechnological approaches to the production of. Shikonin and its analogues have been reported to induce cellcycle arrest, but target information is still unclear. Shikonin and its derivatives are the most abundant naphthoquinone pigments formed in species of the medicinally and economically valuable boraginaceae. Anticancer, antimicrobial and other pharmacological.
Shikonin induces apoptosis and inhibits migration of ovarian. Shikonin production by extractive cultivation in transformed. Shikonin blocks migration and invasion of human breast cancer. Effect of liquid to solid ratio on the yield and purity of shikonin.
To fulfill this, a549 lung cancer cells were treated with shikonin and then. Previous studies have indicated that shikonin inhibits tumor formation, carcinogenesis and metastasis, predominantly by inhibiting the proliferation and induction of apoptosis in tumor cell lines 18. Sensitizing the therapeutic efficacy of taxol with shikonin. Fluorescence microscopy revealed that the intracellular ros levels detected by dcfhda after 2 h of incubation with shikonin were significantly higher in the 6. Enhanced production of target metabolites is essential in order to lower the high production costs involved in the commercial process. These cells are used to inoculate a 750l bioreactor where the shikonin is produced. We hypothesized that shikonin, with a structure similar to that of quinonetype compounds, which are. Shikonin blocks migration and invasion of human breast. Electron microscopy studies suggested that shikonin production was closely associated with the development of elongated rough er and the subsequent formation of electrondense vesicles 0. For the cellular impact of free shk, the cultivated cells in coverslip, at 40%50% confluency, were treated with a designated amount of free shk 5. Shikonin induced cell death neither was inhibited by a pancaspase inhibitor zvadfmk, nor involved translocation of aif fig.
In establishing cell culture, the ammonium ion, and light cycle inhibited shikonin formation. Aug 17, 2017 given that shikonin induced necroptosis is often accompanied by an overproduction of ros 3,14, we examined the relationship between ros production and shikonin dosage. Shikonin inhibits thyroid cancer cell growth and invasiveness. Lithospermum cells are today grown on an industrial scale in a 200l bioreactor with a growth medium, then transferred to a smaller reactor with a medium that promotes shikonin production. Potential and prospects of shikonin production enhancement. Shikonin is a natural compound isolated from herbs and traditional medicines that have been used in a number of countries to treat various illnesses including inflammation, virus infection and cancer for centuries. Recent studies have shown that shikonin demonstrates various bioactivities related to the treatment of cancer, inflammation, and woun. Mmp9 and mmp2 are important ecmdegrading enzymes that are reported to be involved in cancer cell invasion and metastasis.
Fujita y, maeda y, suga c, morimoto t 1983 production of shikonin derivatives by cell suspension cultures of lithospermum erythrorhizon. This study was aimed to investigate whether this chemical could also inhibit cell growth of lung cancer cells and, if so, works via what molecular mechanism. Shikonin, a natural naphthoquinone pigment isolated from lithospermum erythrorhizon, has been reported to suppress growth of various cancer cells. Shikonin is known to selective killing of prostate cancer cell types, while sparing normal cells. Shikonin accumulates in mitochondria and causes a breakdown of the mitochondrial membrane potential. Shikonin induces apoptosis and inhibits migration of.
For germination, the seeds were cultured on growth regulator free ms medium and for. Shikonin and its derivatives are contained in the outer surface of the roots of lithospermum erythrorhizori boraginaceae and these purplered compounds, with naphthazalin skeleton fig. Pharmacological properties of shikonin home thieme connect. Synthesis, biological function and evaluation of shikonin in. Shikonin production with in situ extraction in transformed cell and hairy root cultures by nhexadecane was 7. Pdf biotechnological approaches to the production of shikonins. Enhancement of shikonin production in single and twophase. Characterization of shikonin derivative secretion in title. Induction of apoptosis by shikonin through a rosjnkmediated. Inhibits chemokine receptor function and suppresses hiv1. Apr 07, 2014 shikonin, a smallmolecule natural product which inhibits the activity of pyruvate kinase m2 pkm2, has been studied as an anticancer drug candidate in human cancer models.
Request pdf potential and prospects of shikonin production. It has an appreciable pharmacological effect as an. The dried root is called koshikon and has been used as a crude drug. Adobe acrobat reader dc software is the free global standard for reliably viewing, printing, and commenting on pdf documents. This study examined the signaling events induced by shikonin that lead to the induction of apoptosis in bcrablpositive chronic myelogenous leukemia cml cells e. Phytochemical and morphological evidences for shikonin. Fluids free fulltext comparative study of pegylated and.
It is noteworthy that excessive ros generation caused by shikonin was much more. Displays antiangiogenic properties by inhibition of proliferation and migration of endothelial cells, blocking integrin. Papageorgiou vp aa, couladouros ea, hepworth d, nicolaou kc. Dec 01, 20 the percentage of rospositive cells was increased from 68. Enhancement of shikonin production in single and two.
Shikonin, a natural naphthoquinone, was used in traditional chinese medicine for the treatment of different inflammatory diseases and recent studies revealed the anticancer. Effect of number of extraction cycles on the yield and purity of shikonin. Abandoned application number us11129,255 inventor feixin wang original assignee feixin wang. Potential and prospects of shikonin production enhancement in.
Shikonin, a novel compound isolated from the chinese herbal therapeutic agent zicao, has been demonstrated to exhibit anticancer activity 16,17. A mdamb231 and mcf7 cells were wounded by scratching with a pipette tip and then were incubated with or without 100 nm pma and the indicated concentrations of shikonin. Jun 01, 2020 furthermore, knocking down expression of lepgt1 in l. Frontiers shikonin inhibits cancer through p21 upregulation. Shikonin also inhibits cancer cell glycolysis by targeting tumor pyruvate kinase m2. Shikonin occurs as a natural compound in the herb lithospermum erythrorhizon which has use in chinese herbal medicines.
A key step in the shikonin biosynthetic pathway, namely the c3 hydroxylation of the prenylated phenolic intermediate geranylhydroquinone, is expected to be catalyzed by a cytochrome p450. Characterization of shikonin derivative secretion in. Human breast adenocarcinoma mbamd231 cells, which have higher levels of pkm2 expression. Shikonin, a naphthoquinone red pigment, produced from roots of arnebia hispidissima, a. Shikonin, a naphthoquinone compound, rapidly induces cell. Shikonin increases glucose uptake in skeletal muscle cells. This is the first report on the establishment of isolated cultures of o. The practice of tcm is a holistic approach that includes the use of herbal preparations, acupunctur. Shikonin circumvents cancer drug resistance by induction. After treated with shikonin for 3 h, 42% cells were permeable to. The first commercial production of shikonin by cell culture using lithospermum erythrorhizone in 1983 has attracted the researchers at a global scenario. Frontiers characterization of shikonin derivative secretion. Crystal structure of sarscov2 proteaseinhibitor in complex. On the basis of these observations and the foregoing data, we examined the effect of shikonin on the expression of both mmp2 and mmp9 in mdamb231 cells.
Advantages of cell suspension cultures for production of secondary. Comparative proteomic analysis of lithospermum erythrorhizon. Molecules free fulltext biological effects of shikonin. Ec109 tumor model was established to observe the antitumor effect of shikoninin vivo. Shikonin inhibits cancer cell cycling by targeting cdc25s. Abstract plant cell cultures of lithospermum erythrorhizon were carried out to produce shikonin by in situ extraction and cell immobilization in. The aromatic precursor 4hydroxybenzoic acid 4hb formed via the shikimate and the phenylpropanoid pathway, while the isoprenoid precursor, geranyldiphosphate gpp is derived from the.
Shikonin, a representative secondary metabolite of l. Electron microscopy studies suggested that shikonin production was closely associated with the. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed. Since there was no difference for shikonin production and expression level of leeil1 between ev and wt, and to avoid the transgenic effects of plasmid, three pbi121 vector containing lines i. Shikonin induces glioma cell necroptosis in vitro by ros. Apr 01, 2015 shikonin effectively induces apoptosis, necrosis and necroptosis in cancer cells 10,14,23. Shikonin, a naphthoquinone extracted from the roots of lithospermum erythrorhizon, is a potent antioxidant with antiinflammatory, antiviral and cancerpreventing properties. Comparison of shikonin derivatives of cultured cells and koshikon. Shikoninloaded antibodyarmed nanoparticles for targeted. Shikonin selectively induces apoptosis in human prostate. Transgenic studies reveal the positive role of leeil1 in. Plants are a rich source of valuable chemicals that are used as herbal and modern medicines.
Shikonin is the major bioactive component extracted from the roots of lithospermum erythrorhizon which is also known as zicao in traditional chinese medicine tcm. Us20050222258a1 pharmaceuticals comprising shikonins as. We investigated whether shikonin stimulated gingival tissue wound healing in human gingival fibroblasts hgf. A similar approach was undertaken to examine the morphological changes of the ovcar5 cells treated with free shk or shkloaded nps.
In addition, we evaluated the effects of shikonin on the mitogenactivated protein kinase mapk signaling pathway, which has an important role. Apr 05, 2002 enhancement of shikonin production in single and twophase suspension cultures of lithospermum erythrorhizon cells using lowenergy ultrasound. Shikonin induces colorectal carcinoma cells apoptosis and. Calli grown on ms ammonium ion free medium supplemented with 3. Effects of shikonin on the migration and invasion of human breast cancer cells. Crystal structure of sarscov2 proteaseinhibitor in. Jun 18, 2020 the severe acute respiratory syndrome coronavirus 2 sarscov2 virus has been spreading rampantly over the whole world, infecting millions of people over 8. It was also demonstrated that shikonin has a better potency as a cox inhibitor than alkannin, but also.
Dw was observed in calli cultured on ms ammonium ion free medium supplemented with 3 mgl bap and 0. In continuous mass production, two cycle extraction is suggested and the extracting solution in second cycle also can be used as solvent in the next production batch. Production of shikonin derivatives by cell suspension cultures of. Shikonin induces apoptosis, necrosis, and premature. Industrial production of shikonin and berberine fujita. Effects of methyl jasmonate on shikonin and dihydroechinofuran. Pharmacological properties and derivatives of shikonina.
The number of patents issued in japan shows that secondary metabolites clinched major share of patents during 19751985. Jan 07, 2019 background shikonin, a natural naphthoquinone, is abundant in chinese herb medicine zicao purple gromwell and has a wide range of biological activities, especially for cancer. Shikonin production by callus culture of onosma bulbotrichom as. And now, its connected to the adobe document cloud.
We have established industrial production processes for shikonin and berberine, secondary plant metabolites that have commercial and pharmaceutical uses, and have been producing shikonin commercially since 1983. The biosynthetic pathway of shikonin was investigated by inouye et al. Enhancement of shikonin production in single and twophase suspension cultures of lithospermum erythrorhizon cells using lowenergy ultrasound. Differences in the production of shikonin derivatives by callus and suspension cultures of lithospermum erythrorhizon sieb. Mechanistically, we show that shikonin arrested the cell cycle at the g2m phase, inhibited the erk. This is very interesting since increased calcium levels are considered to be one of the major events in contractionmediated glucose uptake in skeletal muscle 12. Shikonin, an active ingredient of lithospermum erythrorhizon, exerts antiinflammatory and antibacterial effects, and promotes wound healing.
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