Shikonin https://greenmedinfo.com/category/keywords/Shikonin en Inhibition of pyruvate kinase M2 markedly reduces chemoresistance of advanced bladder cancer to cisplatin. https://greenmedinfo.com/article/inhibition-pyruvate-kinase-m2-markedly-reduces-chemoresistance-advanced-bladde n/a PMID:  Sci Rep. 2017 Apr 5 ;7:45983. Epub 2017 Apr 5. PMID: 28378811 Abstract Title:  Inhibition of Pyruvate Kinase M2 Markedly Reduces Chemoresistance of Advanced Bladder Cancer to Cisplatin. Abstract:  Chemoresistance to cisplatin is a principal cause of treatment failure and mortality of advanced bladder cancer (BC). The underlying mechanisms remain unclear, which hinders the development of preventive strategies. Recent data indicate that pyruvate kinase M2 (PKM2), a glycolytic enzyme for Warburg effect, is strongly upregulated in BC. This study explores the role of PKM2 in chemoresistance and whether inhibiting PKM2 augments the chemosensitivity to cisplatin and reduces BC growth and progression. We found that Shikonin binds PKM2 and inhibits BC cell survival in a dose-dependent but pyruvate kinase activity-independent manner. Down-regulation of PKM2 by shRNA blunts cellular responses to shikonin but enhances the responses to cisplatin. Shikonin and cisplatin together exhibit significantly greater inhibition of proliferation and apoptosis than when used alone. Induced cisplatin-resistance is strongly associated with PKM2 overexpression, and cisplatin-resistant cells respond sensitively to shikonin. In syngeneic mice, shikonin and cisplatin together, but not as single-agents, markedly reduces BC growth and metastasis. Based on these data, we conclude that PKM2 overexpression is a key mechanism of chemoresistance of advanced BC to cisplatin. Inhibition of PKM2 via RNAi or chemical inhibitors may be a highly effective approach to overcome chemoresistance and improve the outcome of advanced BC. https://greenmedinfo.com/article/inhibition-pyruvate-kinase-m2-markedly-reduces-chemoresistance-advanced-bladde#comments Bladder Cancer Shikonin Antiproliferative Apoptotic Chemosensitizer Antiproliferative Apoptotic bladder cancer Chemosensitizer Chemotherapeutic Synergy: Cisplatin Dose Response Shikonin In Vitro Study Wed, 03 May 2017 15:21:01 +0000 greenmedinfo 147160 at https://greenmedinfo.com Shikonin and temozolomide may constitute a powerful new tool for Glioblastoma treatment by reducing therapy resistance and tumor recurrence. https://greenmedinfo.com/article/shikonin-and-temozolomide-may-constitute-powerful-new-tool-glioblastoma-treatm n/a PMID:  Cell Oncol (Dordr). 2017 Apr 11. Epub 2017 Apr 11. PMID: 28401486 Abstract Title:  Dual treatment with shikonin and temozolomide reduces glioblastoma tumor growth, migration and glial-to-mesenchymal transition. Abstract:  PURPOSE: Glioblastomas (GBM) comprise 17% of all primary brain tumors. These tumors are extremely aggressive due to their infiltrative capacity and chemoresistance, with glial-to-mesenchymal transition (GMT) proteins playing a prominent role in tumor invasion. One compound that has recently been used to reduce the expression of these proteins is shikonin (SHK), a naphthoquinone with anti-tumor properties. Temozolomide (TMZ), the most commonly used chemotherapeutic agent in GBM treatment, has so far not been studied in combination with SHK. Here, we investigated the combined effects of these two drugs on the proliferation and motility of GBM-derived cells. METHODS: The cytotoxic and proliferative effects of SHK and TMZ on human GBM-derived cells were tested using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), Ki67 staining and BrdU incorporation assays. The migration capacities of these cells were evaluated using a scratch wound assay. The expression levels ofβ3 integrin, metalloproteinases (MMPs) and GMT-associated proteins were determined by Western blotting and immunocytochemistry. RESULTS: We found that GBM-derived cells treated with a combination of SHK and TMZ showed decreases in their proliferation and migration capacities. These decreases were followed by the suppression of GMT through a reduction ofβ3 integrin, MMP-2, MMP-9, Slug and vimentin expression via inactivation of PI3K/AKT signaling. CONCLUSION: From our results we conclude that dual treatment with SHK and TMZ may constitute a powerful new tool for GBM treatment by reducing therapy resistance and tumor recurrence. https://greenmedinfo.com/article/shikonin-and-temozolomide-may-constitute-powerful-new-tool-glioblastoma-treatm#comments Glioblastoma Shikonin Anti-metastatic Antiproliferative Matrix metalloproteinase-2 (MMP-2) inhibitor Matrix metalloproteinase-9 (MMP-9) inhibitor Anti-metastatic Antiproliferative Chemotherapeutic Synergy: Temozolomide Glioblastoma Shikonin Human In Vitro Wed, 03 May 2017 15:01:18 +0000 greenmedinfo 147157 at https://greenmedinfo.com Shikonin attenuated hepatic ischemia/reperfusion injury by inhibiting apoptosis and autophagy. https://greenmedinfo.com/article/shikonin-attenuated-hepatic-ischemiareperfusion-injury-inhibiting-apoptosis-an n/a PMID:  Sci Rep. 2017 Mar 21 ;7:44785. Epub 2017 Mar 21. PMID: 28322249 Abstract Title:  The protective effects of shikonin on hepatic ischemia/reperfusion injury are mediated by the activation of the PI3K/Akt pathway. Abstract:  Hepatic ischemia/reperfusion (I/R) injury, which can result in severe liver injury and dysfunction, occurs in a variety of conditions such as liver transplantation, shock, and trauma. Cell death in hepatic I/R injury has been linked to apoptosis and autophagy. Shikonin plays a significant protective role in ischemia/reperfusion injury. The purpose of the present study was to investigate the protective effect of shikonin on hepatic I/R injury and explore the underlying mechanism. Mice were subjected to segmental (70%) hepatic warm ischemia to induce hepatic I/R injury. Two doses of shikonin (7.5 and 12.5 mg/kg) were administered 2 h before surgery. Balb/c mice were randomly divided into four groups: normal control, I/R, and shikonin preconditioning at two doses (7.5 and 12.5 mg/kg). The serum and liver tissues were collected at three time points (3, 6, and 24 h). Shikonin significantly reduced serum AST and ALT levels and improved pathological features. Shikonin affected the expression of Bcl-2, Bax, caspase 3, caspase 9, Beclin-1, and LC3, and upregulated PI3K and p-Akt compared with the levels in the I/R group. Shikonin attenuated hepatic I/R injury by inhibiting apoptosis and autophagy through a mechanism involving the activation of PI3K/Akt signaling. https://greenmedinfo.com/article/shikonin-attenuated-hepatic-ischemiareperfusion-injury-inhibiting-apoptosis-an#comments Liver Injury: Ischemia/reperfusion Shikonin Anti-Apoptotic Autophagy Inhibitors Hepatoprotective Anti-Apoptotic Autophagy Inhibitors Hepatoprotective Liver Injury: Ischemia/reperfusion Shikonin Animal Study Wed, 03 May 2017 15:54:01 +0000 greenmedinfo 147166 at https://greenmedinfo.com These results indicate that shikonin treatment may prevent the loss of vision associated with diabetic retinopathy. https://greenmedinfo.com/article/these-results-indicate-shikonin-treatment-may-prevent-loss-vision-associated-d n/a PMID:  Sci Rep. 2017 Mar 21 ;7:44985. Epub 2017 Mar 21. PMID: 28322323 Abstract Title:  Anti-inflammatory properties of shikonin contribute to improved early-stage diabetic retinopathy. Abstract:  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 also compared the effects of a high glucose condition combined with hypoxia (1% O2) to a low glucose condition by using retinal pigment epithelial (RPE) cells, which are a crucial component of the outer blood-retinal barrier and the damage is related to retinopathy. In the retina of DM/hypoxic C57BL/6 mice, abnormal a-wave and b-wave activity, yellowish-white spots, hyperfluorescence, and reduced retinal thickness were found using electroretinography (ERG), fundus photography (FP), fundus fluorescein angiography (FFA), and optical coherence tomography (OCT). Shikonin dose-dependently (0.5-50 mg/kg, per os) prevented DM/hypoxia-induced lesions. In eye tissue, administration of shikonin also attenuated DM/hypoxia-induced pre-apoptotic protein BAX expression as well as the production of inflammatory proteins cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). We also demonstrated that shikonin administration rescues high glucose/hypoxia (1% O2)-induced inflammation, decreased junction protein expression, and permeability in RPE cells. These results indicate that shikonin treatment may prevent the loss of vision associated with DR. https://greenmedinfo.com/article/these-results-indicate-shikonin-treatment-may-prevent-loss-vision-associated-d#comments Diabetic Retinopathy Shikonin Anti-Apoptotic Anti-Inflammatory Agents Cyclooxygenase 2 Inhibitors Anti-Apoptotic Anti-Inflammatory Agents Cyclooxygenase 2 Inhibitors Diabetic Retinopathy Shikonin Animal Study In Vitro Study Wed, 03 May 2017 15:37:06 +0000 greenmedinfo 147163 at https://greenmedinfo.com