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https://www.readbyqxmd.com/read/27905569/shikonin-induces-mitochondria-mediated-apoptosis-and-enhances-chemotherapeutic-sensitivity-of-gastric-cancer-through-reactive-oxygen-species
#1
Wenquan Liang, Aizhen Cai, Guozhu Chen, Hongqing Xi, Xiaosong Wu, Jianxin Cui, Kecheng Zhang, Xudong Zhao, Jiyun Yu, Bo Wei, Lin Chen
The prognosis of gastric cancer remains poor due to clinical drug resistance. Novel drugs are urgently needed. Shikonin (SHK), a natural naphthoquinone, has been reported to trigger cell death and overcome drug resistance in anti-tumour therapy. In this study, we investigated the effectiveness and molecular mechanisms of SHK in treatment with gastric cancer. In vitro, SHK suppresses proliferation and triggers cell death of gastric cancer cells but leads minor damage to gastric epithelial cells. SHK induces the generation of intracellular reactive oxygen species (ROS), depolarizes the mitochondrial membrane potential (MMP) and ultimately triggers mitochondria-mediated apoptosis...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27903739/homocysteine-activates-b-cells-via-regulating-pkm2-dependent-metabolic-reprogramming
#2
Jiacheng Deng, Silin Lü, Huiying Liu, Bo Liu, Changtao Jiang, Qingbo Xu, Juan Feng, Xian Wang
The overactivation of immune cells plays an important role in the pathogenesis of hyperhomocysteinemia (HHcy)-accelerated atherosclerosis. Homocysteine (Hcy) activates B cell proliferation and Ab secretion; however, the underlying mechanisms for these effects remain largely unknown. Metabolic reprogramming is critical for lymphocyte activation and effector function. In this study, we showed that Hcy-activated B cells displayed an increase in both oxidative phosphorylation and glycolysis, with a tendency to shift toward the latter, as well as an accumulation of intermediates in the pentose phosphate pathway, to provide energy and biosynthetic substrates for cell growth and function...
November 30, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27864022/shikonin-inhibits-gefitinib-resistant-non-small-cell-lung-cancer-by-inhibiting-trxr-and-activating-the-egfr-proteasomal-degradation-pathway
#3
Xia Li, Xing-Xing Fan, Ze-Bo Jiang, Wings Ty Loo, Xiao-Jun Yao, Elaine Lai-Han Leung, Louis Wc Chow, Liang Liu
Non-small cell lung cancer (NSCLC) is the dominant type of lung cancer. Molecular targeting has highly improved the treatment efficacy of lung cancer, but new challenges have emerged, such as gefitinib-resistance and cancer recurrence. Therefore, new chemotherapeutic agents and treatment strategies are urgently needed. Shikonin is the main active component of a Chinese medicinal plant 'Zi Cao', which has been shown to exhibit powerful anti-cancer activity in certain types of cancer; however, its activity in gefitinib-resistant lung cancer has never been addressed...
November 15, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27855956/selected-secondary-metabolites-in-echium-vulgare-l-populations-from-nonmetalliferous-and-metalliferous-areas
#4
Sławomir Dresler, Ewelina Rutkowska, Wiesław Bednarek, Grzegorz Stanisławski, Tomasz Kubrak, Anna Bogucka-Kocka, Małgorzata Wójcik
The aim of this study was to evaluate the effect of severe environmental conditions prevailing on metalliferous waste heaps and heavy metal-contaminated growth substrates on accumulation of selected secondary metabolites, antioxidant capacity, and heavy metal concentration in two metallicolous (MC, MZ) and one nonmetallicolous (NM) populations of Echium vulgare L. The shoots and the roots of the three studied populations were collected from their natural habitats. Additionally, the plants were cultivated on different growth substrates, i...
November 14, 2016: Phytochemistry
https://www.readbyqxmd.com/read/27793648/shikonin-regulates-c-myc-and-glut1-expression-through-the-mst1-yap1-tead1-axis
#5
Karel Vališ, Pavel Talacko, Valéria Grobárová, Jan Černý, Petr Novák
The general mechanism underlying the tumor suppressor activity of the Hippo signaling pathway remains unclear. In this study, we explore the molecular mechanisms connecting the Hippo signaling pathway with glucose metabolism. We have found that two key regulators of glycolysis, C-MYC and GLUT1, are targets of the Hippo signaling pathway in human leukemia cells. Our results revealed that activation of MST1 by the natural compound shikonin inhibited the expression of GLUT1 and C-MYC. Furthermore, RNAi experiments confirmed the regulation of GLUT1 and C-MYC expression via the MST1-YAP1-TEAD1 axis...
October 25, 2016: Experimental Cell Research
https://www.readbyqxmd.com/read/27746419/the-serum-pdgf-dependent-melanogenic-role-of-the-minute-level-of-the-oncogenic-kinase-pak1-in-melanoma-cells-proven-by-the-highly-sensitive-kinase-assay
#6
Pham Thi Be Tu, Binh Cao Quan Nguyen, Shinkichi Tawata, Cheong-Yong Yun, Eung Gook Kim, Hiroshi Maruta
We previously demonstrated that the oncogenic kinase PAK4, which both melanomas and normal melanocytes express at a very high level, is essential for their melanogenesis. In the present study, using the highly sensitive "Macaroni-Western" (IP-ATP-Glo) kinase assay, we investigated the melanogenic potential of another oncogenic kinase PAK1, which melanoma (B16F10) cells express only at a very minute level. After transfecting melanoma cells with PAK1-shRNA for silencing PAK1 gene, melanin content, tyrosinase activity, and kinase activity of PAK1 were compared between the wild-type and transfectants...
October 17, 2016: Drug Discoveries & Therapeutics
https://www.readbyqxmd.com/read/27703516/shikonin-inhibits-inflammation-and-chondrocyte-apoptosis-by-regulation-of-the-pi3k-akt-signaling-pathway-in-a-rat-model-of-osteoarthritis
#7
Daijie Fu, Xifu Shang, Zhe Ni, Guoguang Shi
Shikonin has previously been shown to have antitumor, anti-inflammatory, antiviral and extensive pharmacological effects. The aim of the present study was to explore whether the protective effect of shikonin is mediated via the inhibition of inflammation and chondrocyte apoptosis, and to elucidate the potential molecular mechanisms in a rat model of osteoarthritis. A model of osteoarthritis was established in healthy male Sprague-Dawley rats and 10 mg/kg/day shikonin was administered intraperitoneally for 4 days...
October 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/27601995/shikonin-inhibits-intestinal-calcium-activated-chloride-channels-and-prevents-rotaviral-diarrhea
#8
Yu Jiang, Bo Yu, Hong Yang, Tonghui Ma
Secretory diarrhea remains a global health burden and causes major mortality in children. There have been some focuses on antidiarrheal therapies that may reduce fluid losses and intestinal motility in diarrheal diseases. In the present study, we identified shikonin as an inhibitor of TMEM16A chloride channel activity using cell-based fluorescent-quenching assay. The IC50 value of shikonin was 6.5 μM. Short-circuit current measurements demonstrated that shikonin inhibited Eact-induced Cl(-) current in a dose-dependent manner, with IC50 value of 1...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27556106/n-end-rule-pathway-inhibition-assists-colon-tumor-regression-via-necroptosis
#9
Pritha Agarwalla, Rajkumar Banerjee
Recent study has shown that N-end rule pathway, an ubiquitin dependent proteolytic system, counteracts cell death by degrading many antisurvival protein fragments like BCLxL, BRCA1, RIPK1, etc. Inhibition of the N-end rule pathway can lead to metabolic stabilization of proapoptotic protein fragments like RIPK1, thereby sensitizing cells to programmed cell death. Receptor interacting serine-threonine protein kinase-1 (RIPK1) is one of the upstream regulators of programmed necrosis known as necroptosis. Necroptosis is particularly gaining attention of cancer biologists as it provides an alternate therapeutic modality to kill cancer cells, which often evolve multiple strategies to circumvent growth inhibition by apoptosis...
2016: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/27554028/online-storage-recycling-counter-current-chromatography-for-preparative-isolation-of-naphthaquinones-from-arnebia-euchroma-royle-johnst
#10
Jian-Ming He, Shi-Yue Zhang, Qing Mu
Counter-current Chromatography (CCC) has gradually become a popular method for preparative separation, especially in natural product isolation. As an effective separation method, one-dimensional (1D) CCC often results in insufficiently resolved peaks, due to limitations in the separation efficiency and peak capacity in an equipment. Therefore, two dimensional (2D)/multi-dimensional (multi-D) CCC strategies with recycling elution mode were developed to achieve successful separation of target compounds. However, the reported 2D or multi-D CCC approaches lead to experimental costs, complicated procedures, higher requirements for equipment, and increased time consumption...
September 16, 2016: Journal of Chromatography. A
https://www.readbyqxmd.com/read/27530748/endogenous-nitric-oxide-accumulation-is-involved-in-the-antifungal-activity-of-shikonin-against-candida-albicans
#11
Zebin Liao, Yu Yan, Huaihuai Dong, Zhenyu Zhu, Yuanying Jiang, Yingying Cao
The aim of the present study was to investigate the role of nitric oxide (NO) in the antifungal activity of Shikonin (SK) against Candida albicans (C. albicans) and to clarify the underlying mechanism. The results showed that the NO donors S-nitrosoglutathione (GSNO) and L-arginine could enhance the antifungal activity of SK, whereas the NO production inhibitor Nω-nitro-L-arginine methyl ester (L-NAME) attenuated antifungal action. Using the fluorescent dye 3-amino,4-aminomethyl-2', 7-difluorescein, diacetate (DAF-FM DA), we found that the accumulation of NO in C...
August 17, 2016: Emerging Microbes & Infections
https://www.readbyqxmd.com/read/27507975/characterization-of-shikonin-derivative-secretion-in-lithospermum-erythrorhizon-hairy-roots-as-a-model-of-lipid-soluble-metabolite-secretion-from-plants
#12
Kanade Tatsumi, Mariko Yano, Kenta Kaminade, Akifumi Sugiyama, Mayuko Sato, Kiminori Toyooka, Takashi Aoyama, Fumihiko Sato, Kazufumi Yazaki
Shikonin derivatives are specialized lipophilic metabolites, secreted in abundant amounts from the root epidermal cells of Lithospermum erythrorhizon. Because they have anti-microbial activities, these compounds, which are derivatives of red naphthoquinone, are thought to serve as a chemical barrier for plant roots. The mechanism by which they are secreted from cells is, however, largely unknown. The shikonin production system in L. erythrorhizon is an excellent model for studying the mechanism by which lipophilic compounds are secreted from plant cells, because of the abundant amounts of these compounds produced by L...
2016: Frontiers in Plant Science
https://www.readbyqxmd.com/read/27499572/inhibition-of-neutrophil-superoxide-generation-by-shikonin-is-associated-with-suppression-of-cellular-ca-2-fluxes
#13
Kimiko Kazumura, Lucia Satiko Yoshida, Akiko Hara, Hiroshi Tsuchiya, Naokazu Morishita, Hirokazu Kawagishi, Tomohito Kakegawa, Yasukatsu Yuda, Hiromi Takano-Ohmuro
Shikonin, an anti-inflammatory compound of "Shikon", inhibits the neutrophil superoxide (O2 (•-)) generation by NADPH oxidase 2 (Nox2); however, the mechanisms of how shikonin affects Nox2 activity remained unclear. We aimed to elucidate the relationship between the inhibition of Nox2 activity and influences on intracellular Ca(2+) concentration ([Ca(2+)]i) by shikonin. For this purpose, we used a simultaneous monitoring system for detecting changes in [Ca(2+)]i (by fluorescence) and O2 (•-) generation (by chemiluminescence) and evaluated the effects of shikonin on neutrophil-like HL-60 cells stimulated with N-formyl-l-methionyl-l-leucyl-l-phenylalanine (fMLP)...
July 2016: Journal of Clinical Biochemistry and Nutrition
https://www.readbyqxmd.com/read/27476618/modulation-of-plasminogen-activator-inhibitor-1-pai-1-by-the-naphthoquinone-shikonin
#14
Tingting Han, Guangping Zhang, Dong Yan, Hong Yang, Tonghui Ma, Zuguang Ye
Plasminogen activator inhibitor-1 (PAI-1) is a key negative regulator of the fibrinolytic system. Elevated levels of PAI-1 are associated with thrombosis and cardiovascular and metabolic diseases. Inhibition of PAI-1 activity represents a new strategy for antithrombotic and antifibrinolysis therapies. In this study, we systematically investigated the inhibitory effect of shikonin on PAI-1 activity. In the chromogenic substrate-based urokinase (uPA)/PAI-1 assay, we found that shikonin inhibited human PAI-1 activity with IC50 values of 30...
September 2016: Fitoterapia
https://www.readbyqxmd.com/read/27467658/shikonin-suppresses-nlrp3-and-aim2-inflammasomes-by-direct-inhibition-of-caspase-1
#15
Jernej Zorman, Petra Sušjan, Iva Hafner-Bratkovič
Shikonin is a highly lipophilic naphtoquinone found in the roots of Lithospermum erythrorhizon used for its pleiotropic effects in traditional Chinese medicine. Based on its reported antipyretic and anti-inflammatory properties, we investigated whether shikonin suppresses the activation of NLRP3 inflammasome. Inflammasomes are cytosolic protein complexes that serve as scaffolds for recruitment and activation of caspase-1, which, in turn, results in cleavage and secretion of proinflammatory cytokines IL-1β and IL-18...
2016: PloS One
https://www.readbyqxmd.com/read/27452907/shikonin-induces-apoptosis-of-lung-cancer-cells-via-activation-of-foxo3a-egr1-sirt1-signaling-antagonized-by-p300
#16
Yun-Ji Jeung, Han-Gyeul Kim, Jiwon Ahn, Ho-Joon Lee, Sae-Bhom Lee, Misun Won, Cho-Rock Jung, Joo-Young Im, Bo-Kyung Kim, Seung-Kiel Park, Myung Jin Son, Kyung-Sook Chung
Shikonin derivatives exert powerful cytotoxic effects including induction of apoptosis. Here, we demonstrate the cytotoxic efficacy of shikonin in vivo in xenograft models, which did not affect body weight as well as its reduction of cell viability in vitro using several non-small cell lung cancer (NSCLC) cell lines. We found that inhibition of AKT by shikonin activated the forkhead box (FOX)O3a/early growth response protein (EGR)1 signaling cascade and enhanced the expression of the target gene Bim, leading to apoptosis in lung cancer cells...
November 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27415599/anti-leukemic-activity-of-shikonin-role-of-erp57-in-shikonin-induced-apoptosis-in-acute-myeloid-leukemia
#17
Rachana Trivedi, Gerhard A Müller, Manohar S Rathore, Durga P Mishra, Hassan Dihazi
BACKGROUND/AIMS: ER-Stress and activation of unfolded protein response belong to the major factors involved in chemoresistance in cancer cells. In this study we investigated the effect of shikonin on the survival of acute myeloid leukemia cells and the role of ER-stress protein ERP57, a protein disulfide isomerase, in improvement of chemotherapy. METHODS: Using MTT assay we studied cytotoxic effects of shikonin on HL-60 cells. The flow cytometry was adopted to examine the shikonin induced mode of cell death in HL-60 cells...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27371806/acetylshikonin-inhibits-growth-of-oral-squamous-cell-carcinoma-by-inducing-apoptosis
#18
Da Jeong Kim, Ji Hye Lee, Hae Ryoun Park, Young Whan Choi
OBJECTIVES: Recently, shikonin derivatives from Lithospermum erythrorhizon have been suggested as potential chemotherapeutic agents against numerous types of cancers in addition to their traditional uses, e.g., as anti-inflammatory agents. Acetylshikonin, one of shikonin derivatives, has also been reported to possess anticancer activity. However, few studies of the effectiveness of acetylshikonin against cancer cells have been conducted, and there are no studies of oral cancers. In this study, we investigated the usefulness of acetylshikonin as a treatment regimen for oral cancers by observing the growth inhibitory function of acetylshikonin and the involved mechanisms...
June 18, 2016: Archives of Oral Biology
https://www.readbyqxmd.com/read/27322220/shikonin-inhibits-the-proliferation-of-human-breast-cancer-cells-by-reducing-tumor-derived-exosomes
#19
Yao Wei, Mingzhen Li, Shufang Cui, Dong Wang, Chen-Yu Zhang, Ke Zen, Limin Li
Shikonin is a naphthoquinone isolated from the traditional Chinese medicine Lithospermum. It has been used in the treatment of various tumors. However, the effects of shikonin on such diseases have not been fully elucidated. In the present study, we detected the exosome release of a breast cancer cell line (MCF-7) with shikonin treatment and found a positive relationship between the level of secreted exosomes and cell proliferation. We next analyzed miRNA profiles in MCF-7 cells and exosomes and found that some miRNAs are specifically sorted and abundant in exosomes...
2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27293314/shikonin-attenuates-concanavalin-a-induced-acute-liver-injury-in-mice-via-inhibition-of-the-jnk-pathway
#20
Tong Liu, Yujing Xia, Jingjing Li, Sainan Li, Jiao Feng, Liwei Wu, Rong Zhang, Shizan Xu, Keran Cheng, Yuqing Zhou, Shunfeng Zhou, Weiqi Dai, Kan Chen, Fan Wang, Jie Lu, Yingqun Zhou, Chuanyong Guo
OBJECTIVE: Shikonin possesses anti-inflammatory effects. However, its function in concanavalin A-induced acute liver injury remains uncertain. The aim of the present study was to investigate the functions of shikonin and its mechanism of protection on ConA-induced acute liver injury. MATERIALS AND METHODS: Balb/C mice were exposed to ConA (20 mg/kg) via tail vein injection to establish acute liver injury; shikonin (7.5 mg/kg and 12.5 mg/kg) was intraperitoneally administered 2 h before the ConA injection...
2016: Mediators of Inflammation
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