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https://www.readbyqxmd.com/read/29758466/structural-dynamics-and-quantum-mechanical-aspects-of-shikonin-derivatives-as-crebbp-bromodomain-inhibitors
#1
Sarmistha Mitra, Raju Dash
The Proteins involved in the chemical modification of lysine residues in histone, is currently being excessively focused as the therapeutic target for the treatment of cell related diseases like cancer. Among these proteins, the epigenetic reader, CREB-binding protein (CREBBP) bromodomain is one of the most prominent targets for effective anticancer drug design, which is responsible for the reorganization of acetylated histone lysine residues. Therefore, this study employed an integrative approach of structure based drug design, in combination with Molecular Dynamics (MD) and QM/MM study to identify as well as to describe the binding mechanism of two shikonin derivatives, acetylshikonin and propionylshikonin as inhibitors of CREBBP bromodomain...
May 4, 2018: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/29738778/shikonin-enhances-sensitization-of-gefitinib-against-wild-type-egfr-non-small-cell-lung-cancer-via-inhibition-pkm2-stat3-cyclind1-signal-pathway
#2
Jian-Cai Tang, Yong-Gang Ren, Jia Zhao, Feng Long, Jian-Ye Chen, Zhen Jiang
AIMS: Mutant EGFR Non-small cell lung cancer has benefit from gefitinib, but it has limited effect for wild-type EGFR tumors. Shikonin, a natural naphthoquinone isolated from a traditional Chinese medicine, the plant Lithospermum erythrorhizon (zicao), not only can inhibit the tumor growth, but also overcome cancer drug resistance. Our aim is to investigate whether shikonin can enhance antitumor effect of gefitinib in EGFR wild-type lung cancer cells in vitro and in vivo. MATERIALS AND METHODS: CCK-8 was used to determine the proliferation of EGFR wild-type non-small cell lung cancer...
May 5, 2018: Life Sciences
https://www.readbyqxmd.com/read/29725454/shikonin-vitamin-k-3-and-vitamin-k-5-inhibit-multiple-glycolytic-enzymes-in-mcf-7-cells
#3
Jing Chen, Xun Hu, Jingjie Cui
Glycolysis is the most important source of energy for the production of anabolic building blocks in cancer cells. Therefore, glycolytic enzymes are regarded as potential targets for cancer treatment. Previously, naphthaquinones, including shikonin, vitamin K3 and vitamin K5 , have been proven to decrease the rate of glycolysis in cancer cells, which is partly due to suppressed pyruvate kinase activity. In the present study, enzymatic assays were performed using MCF-7 cell lysate in order to screen the profile of glycolytic enzymes in cancer cells inhibited by shikonin, vitamin K3 and vitamin K5 , in addition to pyruvate kinase...
May 2018: Oncology Letters
https://www.readbyqxmd.com/read/29720825/determination-of-five-chemical-markers-in-df-formula-the-herbal-composition-of-ephedra-intermedia-rheum-palmatum-and-lithospermum-erythrorhizon-using-high-performance-liquid-chromatography-ultraviolet-detection
#4
Birang Jeong, Jong Seong Roh, Michung Yoon, Yoosik Yoon, Soon Shik Shin, Hyun Joo Cho, Yong Soo Kwon, Heejung Yang
Background: DF formula is a herbal preparation comprised three medicinal herbs, namely, Ephedra intermedia , Rheum palmatum , and Lithospermum erythrorhizon , which is being used for the treatment of obesity and liver fibrosis in Korean local clinics. Objective: Since the abovementioned three herbs exist with different proportions in DF formula and their chemical markers have different physiochemical properties; it is quite challenging to develop an analytical methodology for the determination of these chemical markers...
April 2018: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/29629826/cure-of-human-diabetic-neuropathy-by-hplc-validated-bark-extract-of-onosma-echioides-l-root
#5
Ambreen Shoaib, Rakesh Kumar Dixit, Badruddeen, Md Azizur Rahman, Paramdeep Bagga, Sarjeel Kaleem, Sahabjada Siddiqui, Md Arshad, Hefazat Hussain Siddiqui
HPLC validated hexane bark extract of Onosma echioides L. root (OE) was evaluated for cure of human diabetic neuropathy in human neuroblastoma cell line. HPLC analysis was performed. Human neuroblastoma cells were grouped into control, normal glucose, high glucose (HG) and HG plus different concentrations of OE extract (10, 25 and 50 μg/mL). MTT, DCFH-DA staining and nuclear condensation assays were performed on neuroblastoma cells to evaluate antiproliferative activity, ROS activity level and apoptotic effect of OE...
April 9, 2018: Natural Product Research
https://www.readbyqxmd.com/read/29608987/rip1-and-rip3-contribute-to-shikonin-induced-glycolysis-suppression-in-glioma-cells-via-increase-of-intracellular-hydrogen-peroxide
#6
Bin Lu, Zongqi Wang, Ye Ding, Xuanzhong Wang, Shan Lu, Chongcheng Wang, Chuan He, Meihua Piao, Guangfan Chi, Yinan Luo, Pengfei Ge
RIP1 and RIP3 are necroptosis initiators, but their roles in regulation of glycolysis remain elusive. In this study, we found shikonin activated RIP1 and RIP3 in glioma cells in vitro and in vivo, which was accompanied with glycolysis suppression. Further investigation revealed that shikonin-induced decreases of glucose-6-phosphate and pyruvate and downregulation of HK II and PKM2 were significantly prevented when RIP1 or RIP3 was pharmacologically inhibited or genetically knocked down with SiRNA. Moreover, shikonin also triggered accumulation of intracellular H2 O2 and depletion of GSH and cysteine...
March 30, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29563994/shikonin-induces-mitochondria-mediated-apoptosis-and-attenuates-epithelial-mesenchymal-transition-in-cisplatin-resistant-human-ovarian-cancer-cells
#7
Kristina Shilnikova, Mei Jing Piao, Kyoung Ah Kang, Yea Seong Ryu, Jeong Eon Park, Yu Jae Hyun, Ao Xuan Zhen, Yong Joo Jeong, Uhee Jung, In Gyu Kim, Jin Won Hyun
Cisplatin-based chemotherapy often results in the development of chemoresistance when used to treat ovarian cancer, which is difficult to overcome. The present study investigated the cytotoxic and anti-migratory effects of shikonin, a naphthoquinone compound, on cisplatin-resistant human ovarian cancer A2780 cells (A2780-CR). Shikonin had a potent dose-dependent cytotoxic effect on A2780-CR cells, with 9 µM shikonin treatment reducing A2780-CR cell viability by 50%, validate using an MTT assay. Shikonin induced apoptosis, as evidenced by the increased number of apoptotic bodies, following staining with Hoechst 33342, and terminal deoxynucleotidyl cell transferase dUTP nick end labeling-positive cells following treatment...
April 2018: Oncology Letters
https://www.readbyqxmd.com/read/29549685/the-traditional-medicine-aspects-biological-activity-and-phytochemistry-of-arnebia-spp
#8
Amirsaeed Hosseini, Fatemeh Mirzaee, Ali Davoodi, Hossein Bakhshi Jouybari, Mohammad Azadbakh
Arnebia, a sub cosmopolitan and important genus of the Boraginaceae family, comprises 25 species distributed among the world. Based on the studies of Persian medicine texts, there are some promising bioactivities for this genus that is unknown in modern medicine and some of them are still the basis of new remedies. This article presents Arnebia according to the most important ancient information by the most famous Persian medicine books like Makhzan Al Advieh, Tohfat Al-Momenin, Al-Qanun, Al-Seidaneh and Ekhtiarate Badiei...
February 1, 2018: Medicinski Glasnik
https://www.readbyqxmd.com/read/29507626/sarcoma-targeting-peptide-decorated-polypeptide-nanogel-intracellularly-delivers-shikonin-for-upregulated-osteosarcoma-necroptosis-and-diminished-pulmonary-metastasis
#9
Suoyuan Li, Tao Zhang, Weiguo Xu, Jianxun Ding, Fei Yin, Jing Xu, Wei Sun, Hongsheng Wang, Mengxiong Sun, Zhengdong Cai, Yingqi Hua
PURPOSE: Osteosarcoma is the most common primary bone cancer and is notorious for pulmonary metastasis, representing a major threat to pediatric patients. An effective drug targeting osteosarcoma and its lung metastasis is urgently needed. DESIGN: In this study, a sarcoma-targeting peptide-decorated disulfide-crosslinked polypeptide nanogel (STP-NG) was exploited for enhanced intracellular delivery of shikonin (SHK), an extract of a medicinal herb, to inhibit osteosarcoma progression with minimal systemic toxicity...
2018: Theranostics
https://www.readbyqxmd.com/read/29472576/broad-blocking-of-mdr-efflux-pumps-by-acetylshikonin-and-acetoxyisovalerylshikonin-to-generate-hypersensitive-phenotype-of-malignant-carcinoma-cells
#10
Seyed Abbas Mirzaei, Somayeh Reiisi, Parmida Ghiasi Tabari, Abolfazl Shekari, Fatemeh Aliakbari, Elaheh Azadfallah, Fatemeh Elahian
Cytotoxic activities of acetylshikonin and acetoxyisovalerylshikonin alone and in combination with chemotherapeutic agents against parental and drug resistant cell lines were determined using the MTT assay. Effects of Shikonin derivatives on BCRP, MDR1 and MRP transcript and protein levels were relatively measured. Finally, accumulation and efflux kinetics were conducted. The results revealed cell- and concentration-dependency of the cell cytotoxicity. Acetylshikonin and acetoxyisovalerylshikonin transiently made the mRNA ocean turbulent, but FACS analyses using fluorescent-labeled antibodies showed no significant change in the MDR-protein levels...
February 22, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29468758/evidence-for-shikonin-acting-as-an-active-inhibitor-of-human-carboxylesterases-2-implications-for-herb-drug-combination
#11
Jia-Nan Li, Yun-Feng Cao, Rong-Rong He, Guang-Bo Ge, Bin Guo, Jing-Jing Wu
Shikonin, a natural naphthoquinone compound derived from the herb Lithospermum erythrorhizon, is widely used for its various pharmacological activities. However, its potential interactions with other medications by inhibiting human carboxylesterases 2 (hCE2) remain unknown. In this study, the inhibitory effects of shikonin on the activity of hCE2 in human liver microsomes are investigated by using fluorescein diacetate (FD), N-(2-butyl-1,3-dioxo-2,3-dihydro-1H-phenalen-6-yl)-2-chloroacetamide (NCEN), and CPT-11 as substrates of hCE2...
February 22, 2018: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/29463831/shikonin-exerts-antitumor-activity-in-burkitt-s-lymphoma-by-inhibiting-c-myc-and-pi3k-akt-mtor-pathway-and-acts-synergistically-with-doxorubicin
#12
Fan Ni, Xianbo Huang, Zhenzhen Chen, Wenbin Qian, Xiangmin Tong
Burkitt's lymphoma (BL) is a highly aggressive malignancy molecularly characterized by deregulation of the C-MYC proto-oncogene. Recently, it has been confirmed that phosphatidylinositol-3-kinase (PI3K) pathway activation is a crucial element in the malignant transformation of the B cells in BL. Despite the better outcome of adults with BL treated with high-intensity chemotherapy regimens, the overall survival rate for patients older than 60 years remains dismal. Shikonin, a natural naphthoquinone derived from Chinese herbal medicine plant, has the potential to induce cell death in a series of human cancer...
February 20, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29449346/shikonin-suppresses-proliferation-and-induces-apoptosis-in-endometrioid-endometrial-cancer-cells-via-modulating-mir-106b-pten-akt-mtor-signaling-pathway
#13
Caimei Huang, Guohua Hu
Shikonin, a natural naphthoquinone isolated from a traditional Chinese medicinal herb, which exerts anticancer effects in various cancers. However, the molecular mechanisms underlying the therapeutic effects of shikonin against endometrioid endometrial cancer (EEC) have not yet been fully elucidated. Herein, we investigated anticancer effects of shikonin on EEC cells and explored the underlying molecular mechanism. We observed that shikonin inhibits proliferation in human EEC cell lines in a dose-dependent manner...
April 27, 2018: Bioscience Reports
https://www.readbyqxmd.com/read/29434733/shikonin-causes-apoptosis-by-disrupting-intracellular-calcium-homeostasis-and-mitochondrial-function-in-human-hepatoma-cells
#14
Hui Wang, Zheng Liu, Xiangchen Li, Ruijie Zhao, Yabin Pu, Handong Wu, Weijun Guan
Shikonin is known to suppress proliferation and induce apoptosis in a variety of cancer cell lines. In the present study, SMMC-7721 human hepatocellular carcinoma cells were treated with shikonin (1, 2 or 4 µM) for 12-48 h. Cell morphological alterations and DNA damage were determined. Furthermore, changes in cell cycle, mitochondrial transmembrane potential, calcium homeostasis and levels of reactive oxygen species were measured. Shikonin-treated SMMC-7721 cells exhibited morphological changes and DNA damage...
February 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29422643/rna-seq-transcriptome-analysis-of-breast-cancer-cell-lines-under-shikonin-treatment
#15
Kuo-Hua Lin, Ming-Yii Huang, Wei-Chung Cheng, Shu-Chi Wang, Shih-Hua Fang, Hung-Pin Tu, Chia-Cheng Su, Yung-Li Hung, Po-Len Liu, Chi-Shuo Chen, Yu-Ting Wang, Chia-Yang Li
Shikonin is a naphthoquinone isolated from the dried root of Lithospermum erythrorhizon, an herb used in Chinese medicine. Although several studies have indicated that shikonin exhibits antitumor activity in breast cancer, the mechanism of action remains unclear. In the present study, we performed transcriptome analysis using RNA-seq and explored the mechanism of action of shikonin in regulating the growth of different types of breast cancer cells. The IC50 of shikonin on MCF-7, SKBR-3 and MDA-MB-231 cells were 10...
February 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29414119/shikonin-upregulates-the-expression-of-drug-metabolizing-enzymes-and-drug-transporters-in-primary-rat-hepatocytes
#16
Chin-Shiu Huang, Haw-Wen Chen, Tzu-Yu Lin, Ai-Hsuan Lin, Chong-Kuei Lii
ETHNOPHARMACOLOGICAL RELEVANCE: Shikonin, a naphthoquinone pigment abundant in the root of the Chinese herb Lithospermum erythrorhizon, has been widely used to treat inflammatory diseases for thousands of years. Whether shikonin changes drug metabolism remains unclear. AIM OF THE STUDY: We investigated whether shikonin modulates the expression of hepatic drug-metabolizing enzymes and transporters as well as the possible mechanisms of this action. MATERIALS AND METHODS: Primary hepatocytes isolated from Sprague-Dawley rats were treated with 0-2 μM shikonin and the protein and mRNA levels of drug-metabolizing enzymes and transporters as well as the activation of aryl hydrocarbon receptor (AhR) and NF-E2-related factor 2 (Nrf2) were determined...
April 24, 2018: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29394289/lapachol-inhibits-glycolysis-in-cancer-cells-by-targeting-pyruvate-kinase-m2
#17
Mani Shankar Babu, Sailendra Mahanta, Alexander J Lakhter, Takashi Hato, Subhankar Paul, Samisubbu R Naidu
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 structural analog shikonin, a known inhibitor of PKM2, lapachol failed to induce non-apoptotic cell death ferroxitosis in hypoxia. However, melanoma cells treated with lapachol showed a dose-dependent inhibition of glycolysis and a corresponding increase in oxygen consumption...
2018: PloS One
https://www.readbyqxmd.com/read/29389913/shikonin-inhibites-migration-and-invasion-of-thyroid-cancer-cells-by-downregulating-dnmt1
#18
Yue Zhang, Bin Sun, Zhi Huang, Dai-Wei Zhao, Qingfan Zeng
BACKGROUND Shikonin is a component of Chinese herbal medicine. The aim of this study was to investigate the effects of shikonin on cell migration of papillary thyroid cancer cells of the TPC-1 cell line in vitro and expression levels of the phosphate and tensin homolog deleted on chromosome 10 (PTEN) and DNA methyltransferase 1 (DNMT1) genes. MATERIAL AND METHODS The Cell Counting Kit-8 (CCK-8) assay was performed to evaluate the proliferation of TPC-1 papillary thyroid cancer cells, and the normal thyroid cells, HTori-3, in vitro...
February 1, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29382149/anticancer-efficacy-of-targeted-shikonin-liposomes-modified-with-rgd-in-breast-cancer-cells
#19
Xianchun Wen, Jiping Li, Defu Cai, Liling Yue, Qi Wang, Li Zhou, Li Fan, Jianwen Sun, Yonghui Wu
Shikonin (SHK) has been proven to have a good anti-tumor effect. However, poor water solubility and low bioavailability limit its wide application in clinical practice. In this study, to overcome these drawbacks, RGD-modified shikonin-loaded liposomes (RGD-SSLs-SHK) were successfully prepared. It exhibited excellent physicochemical characteristics including particle size, zeta potential, encapsulation efficiency, and delayed release time. Meanwhile, the targeting activity of the RGD-modified liposomes was demonstrated by flow cytometry and confocal microscopy in the αv β₃-positive MDA-MB-231 cells...
January 29, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29312593/shikonin-induces-ros-based-mitochondria-mediated-apoptosis-in-colon-cancer
#20
Wenquan Liang, Jianxin Cui, Kecheng Zhang, Hongqing Xi, Aizhen Cai, Jiyang Li, Yunhe Gao, Chong Hu, Yi Liu, Yixun Lu, Ning Wang, Xiaosong Wu, Bo Wei, Lin Chen
Colon cancer is the third most common malignancy worldwide, and chemotherapy is a widely used strategy in clinical therapy. Chemotherapy-resistant of colon cancer is the main cause of recurrence and progression. Novel drugs with efficacy and safety in treating colon cancer are urgently needed. Shikonin, a naphthoquinone derived from the roots of the herbal plant Lithospermum erythrorhizon , has been determined to be a potent anti-tumor agent. The aim of the present study was to detect the underlying anti-tumor mechanism of shikonin in colon cancer...
December 12, 2017: Oncotarget
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