β-Elemene Synergizes With Gefitinib to Inhibit Stem-Like Phenotypes and Progression of Lung Cancer via Down-Regulating EZH2.


:The inhibitors for EGF receptor tyrosine kinase (EGFR-TKIs) such as gefitinib have been used as a standard treatment for non-small cell lung cancer (NSCLC), but the increasingly occurrence of drug resistance, the associated adverse effects and the enrichment of cancer stem cells significantly impedes its clinical application. β-elemene is a natural sesquiterpene with potent anti-cancer ability, and also it is renowned for its plant-origin, safety and the additive effect with traditional therapies, which prompt us to explore its potential to co-operate with TKIs to achieve greater therapeutic efficacy. Impressively, our study demonstrates that, elemene, in combination of gefitinib, displayed a significantly higher activity in inhibiting lung cancer cellular proliferation, migration and invasion. More importantly, combinative treatment profoundly impaired the epithelial to mesenchymal transition (EMT), the stem-like properties and the self-renewal capacity of lung cancer cells, and hence impeded the in vivo tumor development. We also reveal that the synergistic anti-tumor effect of elemene and gefitinib was largely mediated their regulation of enhancer of zeste homolog 2 (EZH2), an oncogenic histone methyltransferase and gene transcriptional regulator. Thus, our data indicate that combinative treatment of elemene and gefitinib has greater anti-neoplastic activity and greater efficacies in targeting cancer stem-like properties, mainly through regulating the malignant gene modifier and hence the subsequent effector molecules required for cancer progression. The findings may have potential implications for treating aggressive and resistant lung cancers.


Front Pharmacol


Cheng H,Ge X,Zhuo S,Gao Y,Zhu B,Zhang J,Shang W,Xu D,Ge W,Shi L




Has Abstract


2018-11-30 00:00:00








  • Salvianolic Acid B Inhibits Activation of Human Primary Hepatic Stellate Cells Through Downregulation of the Myocyte Enhancer Factor 2 Signaling Pathway.

    abstract::Various isoforms of myocyte enhancer factor 2 (MEF2) have been shown to play a role in the activation of rat hepatic stellate cells (HSCs) in culture. The signals that regulate MEF2 in HSCs are unknown. In addition, whether MEF2s regulate the activation of human HSCs (H-HSCs) is unclear. Here, we studied the expressio...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章


    authors: Zhang W,Ping J,Zhou Y,Chen G,Xu L

    更新日期:2019-04-11 00:00:00

  • Protein kinases as switches for the function of upstream stimulatory factors: implications for tissue injury and cancer.

    abstract::The upstream stimulatory factors (USFs) are regulators of important cellular processes. Both USF1 and USF2 are supposed to have major roles in metabolism, tissue protection and tumor development. However, the knowledge about the mechanisms that control the function of USFs, in particular in tissue protection and cance...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章


    authors: Horbach T,Götz C,Kietzmann T,Dimova EY

    更新日期:2015-02-18 00:00:00

  • Animal Toxins as Therapeutic Tools to Treat Neurodegenerative Diseases.

    abstract::Neurodegenerative diseases affect millions of individuals worldwide. So far, no disease-modifying drug is available to treat patients, making the search for effective drugs an urgent need. Neurodegeneration is triggered by the activation of several cellular processes, including oxidative stress, mitochondrial impairme...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章,评审


    authors: de Souza JM,Goncalves BDC,Gomez MV,Vieira LB,Ribeiro FM

    更新日期:2018-02-23 00:00:00

  • Cellular Cholesterol Distribution Influences Proteolytic Release of the LRP-1 Ectodomain.

    abstract::Low-density lipoprotein receptor-related protein-1 (LRP-1) is a multifunctional matricellular receptor composed of a large ligand-binding subunit (515-kDa α-chain) associated with a short trans-membrane subunit (85-kDa β-chain). LRP-1, which exhibits both endocytosis and cell signaling properties, plays a key role in ...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章


    authors: Dekky B,Wahart A,Sartelet H,Féré M,Angiboust JF,Dedieu S,Piot O,Devy J,Emonard H

    更新日期:2016-02-12 00:00:00

  • Chidamide Inhibits Acute Myeloid Leukemia Cell Proliferation by lncRNA VPS9D1-AS1 Downregulation via MEK/ERK Signaling Pathway.

    abstract::Irregular histone modification and aberrant lncRNAs expression are closely related to the occurrence of tumors including acute myeloid leukemia (AML). However, the effects and specific underlying molecular mechanism of histone deacetylase inhibitors on lncRNA expression in AML cells are unclear. Here, we reported the ...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章


    authors: Lin L,Que Y,Lu P,Li H,Xiao M,Zhu X,Li D

    更新日期:2020-10-19 00:00:00

  • Traditional Chinese Medicine Regulating Lymphangiogenesis: A Literature Review.

    abstract::Lymphatic vessels, as an important part of the lymphatic system, form a fine vascular system in humans and play an important role in regulating fluid homeostasis, assisting immune surveillance and transporting dietary lipids. Dysfunction of lymphatic vessels can cause many diseases, including cancer, cardiovascular di...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章,评审


    authors: Peng L,Dong Y,Fan H,Cao M,Wu Q,Wang Y,Zhou C,Li S,Zhao C,Wang Y

    更新日期:2020-09-03 00:00:00

  • The Grass Might Be Greener: Medical Marijuana Patients Exhibit Altered Brain Activity and Improved Executive Function after 3 Months of Treatment.

    abstract::The vast majority of states have enacted full or partial medical marijuana (MMJ) programs, causing the number of patients seeking certification for MMJ use to increase dramatically in recent years. Despite increased use of MMJ across the nation, no studies thus far have examined the specific impact of MMJ on cognitive...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章


    authors: Gruber SA,Sagar KA,Dahlgren MK,Gonenc A,Smith RT,Lambros AM,Cabrera KB,Lukas SE

    更新日期:2018-01-17 00:00:00

  • A Guide to PIN1 Function and Mutations Across Cancers.

    abstract::PIN1 is a member of a family of peptidylprolyl isomerases that bind phosphoproteins and catalyze the rapid cis-trans isomerization of proline peptidyl bonds, resulting in an alteration of protein structure, function, and stability. PIN1 is overexpressed in human cancers, suggesting it promotes tumorigenesis, but depen...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章


    authors: El Boustani M,De Stefano L,Caligiuri I,Mouawad N,Granchi C,Canzonieri V,Tuccinardi T,Giordano A,Rizzolio F

    更新日期:2019-01-22 00:00:00

  • A Rare Class of New Dimeric Naphthoquinones from Diospyros lotus have Multidrug Reversal and Antiproliferative Effects.

    abstract::Three new dimeric naphthoquinones, 5,4'-dihydroxy-1'-methoxy-6,6'-dimethyl-7,3'-binaphthyl-1,4,5',8'-tetraone (1), 5',8'-dihydroxy-5-methoxy-6,6'-dimethyl-7,3'-binaphthyl-1,4,1',4'-tetraone (2) and 8,5',8'-trihydroxy-6,6'-dimethyl-7,3'-binaphthyl-1,4,1',4'-tetraone (3), were isolated from the roots of Diospyros lotus....

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章


    authors: Rauf A,Uddin G,Siddiqui BS,Molnár J,Csonka Á,Ahmad B,Szabó D,Farooq U,Khan A

    更新日期:2015-12-16 00:00:00

  • Apatinib Combined With SOX Regimen in Conversion Treatment of Advanced Gastric Cancer: A Case Series and Literature Review.

    abstract::Gastric cancer is a common digestive tract tumor and the second most prevalent cancer. The prognosis of advanced gastric cancer is poor. Conversion therapy can reduce tumor burden, downgrade tumor, and increase the possibility of complete resection, thus prolonging the survival time of patients with gastric cancer. In...

    journal_title:Frontiers in pharmacology



    authors: Jiang D,Xu Y,Chen Y,Jiang J,Wang M,Yang M,Chen Z,Yang L

    更新日期:2020-07-14 00:00:00

  • Triple-Gene Therapy for Stroke: A Proof-of-Concept in Vivo Study in Rats.

    abstract::Natural brain repair after stroke is extremely limited, and current therapeutic options are even more scarce with no clinical break-through in sight. Despite restricted regeneration in the central nervous system, we have previously proved that human umbilical cord blood mono-nuclear cells (UCB-MC) transduced with aden...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章


    authors: Sokolov ME,Bashirov FV,Markosyan VA,Povysheva TV,Fadeev FO,Izmailov AA,Kuztetsov MS,Safiullov ZZ,Shmarov MM,Naroditskyi BS,Palotás A,Islamov RR

    更新日期:2018-02-15 00:00:00

  • Antidepressant activity: contribution of brain microdialysis in knock-out mice to the understanding of BDNF/5-HT transporter/5-HT autoreceptor interactions.

    abstract::Why antidepressants vary in terms of efficacy is currently unclear. Despite the leadership of selective serotonin reuptake inhibitors (SSRIs) in the treatment of depression, the precise neurobiological mechanisms involved in their therapeutic action are poorly understood. A better knowledge of molecular interactions b...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章


    authors: Gardier AM

    更新日期:2013-08-08 00:00:00

  • The Use of Beta Blockers in Takotsubo Syndrome as Compared to Acute Coronary Syndrome.

    abstract:Background:Takotsubo syndrome (TTS) and acute coronary syndrome (ACS) patients have a similar mortality rate. In this study, we sought to determine the short- and long-term outcome of TTS patients as compared to ACS patients both treated with beta-blockers. Objectives:In the present study we described the data of 5 ye...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章


    authors: Kummer M,El-Battrawy I,Gietzen T,Ansari U,Behnes M,Lang S,Zhou X,Borggrefe M,Akin I

    更新日期:2020-05-14 00:00:00

  • Histone Methyltransferases as Therapeutic Targets for Kidney Diseases.

    abstract::Emerging evidence has demonstrated that epigenetic regulation plays a vital role in gene expression under normal and pathological conditions. Alterations in the expression and activation of histone methyltransferases (HMTs) have been reported in preclinical models of multiple kidney diseases, including acute kidney in...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章,评审


    authors: Yu C,Zhuang S

    更新日期:2019-12-06 00:00:00

  • Growth Pattern in Chinese Children With 5α-Reductase Type 2 Deficiency: A Retrospective Multicenter Study.

    abstract:Background:5α-reductase type 2 deficiency (5αRD) is an autosomal recessive hereditary disease of the group of 46, XY disorders of sex development (DSD). Objective:To study the growth pattern in Chinese pediatric patients with 5αRD. Subjects:Data were obtained from 141 patients with 5αRD (age: 0-16 years old) who visi...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章


    authors: Zhao X,Song Y,Chen S,Wang X,Luo F,Yang Y,Chen L,Chen R,Chen H,Su Z,Wu D,Gong C

    更新日期:2019-03-15 00:00:00

  • ATC-NLSP: Prediction of the Classes of Anatomical Therapeutic Chemicals Using a Network-Based Label Space Partition Method.

    abstract::Anatomical Therapeutic Chemical (ATC) classification system proposed by the World Health Organization is a widely accepted drug classification scheme in both academic and industrial realm. It is a multilabeling system which categorizes drugs into multiple classes according to their therapeutic, pharmacological, and ch...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章


    authors: Wang X,Wang Y,Xu Z,Xiong Y,Wei DQ

    更新日期:2019-09-05 00:00:00

  • IL-6 but Not TNFα Levels Are Associated With Time to Pregnancy in Female Rheumatoid Arthritis Patients With a Wish to Conceive.

    abstract::Fertility issues are common amongst women with rheumatoid arthritis (RA). Interleukin 6 (IL-6) and tumor necrosis factor alpha (TNFα), known key players in RA pathogenesis, have been associated with reproductive disorders. This study investigates the role of these cytokines in decreased fertility in women with active ...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章


    authors: Bongenaar M,Smeele HTW,Lubberts E,Dolhain RJEM

    更新日期:2020-12-10 00:00:00

  • Chemical Composition of Scrophularia lucida and the Effects on Tumor Invasiveness in Vitro.

    abstract::A detannified methanolic extract of Scrophularia lucida L. attenuated the formation of cancer cell-induced circular chemorepellent induced defects (CCIDs) in the lymph endothelial cell barrier, which resemble entry ports for the intravasating tumor into the vasculature as a prerequisite for lymph node metastasis. Ther...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章


    authors: Lewenhofer V,Schweighofer L,Ledermüller T,Eichsteininger J,Kählig H,Zehl M,Nguyen CH,Krupitza G,Özmen A,Krenn L

    更新日期:2018-04-03 00:00:00

  • Fusogenic Liposomes Increase the Antimicrobial Activity of Vancomycin Against Staphylococcus aureus Biofilm.

    abstract::Objective: The aim of the present study was to encapsulate vancomycin in different liposomal formulations and compare the in vitro antimicrobial activity against Staphylococcus aureus biofilms. Methods: Large unilamellar vesicles of conventional (LUV VAN), fusogenic (LUVfuso VAN), and cationic (LUVcat VAN) liposomes e...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章


    authors: Scriboni AB,Couto VM,Ribeiro LNM,Freires IA,Groppo FC,de Paula E,Franz-Montan M,Cogo-Müller K

    更新日期:2019-11-29 00:00:00

  • Antidepressant and Anti-Neuroinflammatory Effects of Bangpungtongsung-San.

    abstract::Bangpungtongsung-san (BTS) is a traditional Korean medicine consisting of 18 herbs, some which have antidepressant effects. Here, we used an animal model of reserpine-induced depression and lipopolysaccharide (LPS)-stimulated BV2 microglia to assess the antidepressant and anti-neuroinflammatory effects of BTS. Aside f...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章


    authors: Park BK,Kim NS,Kim YR,Yang C,Jung IC,Jang IS,Seo CS,Choi JJ,Lee MY

    更新日期:2020-07-10 00:00:00

  • Artificial Intelligence-Based Multiclass Classification of Benign or Malignant Mucosal Lesions of the Stomach.

    abstract::Gastric cancer (GC) is one of the leading causes of cancer-related death worldwide. It takes some time from chronic gastritis to develop in GC. Early detection of GC will help patients obtain timely treatment. Understanding disease evolution is crucial for the prevention and treatment of GC. Here, we present a convolu...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章


    authors: Ma B,Guo Y,Hu W,Yuan F,Zhu Z,Yu Y,Zou H

    更新日期:2020-10-02 00:00:00

  • AIPpred: Sequence-Based Prediction of Anti-inflammatory Peptides Using Random Forest.

    abstract::The use of therapeutic peptides in various inflammatory diseases and autoimmune disorders has received considerable attention; however, the identification of anti-inflammatory peptides (AIPs) through wet-lab experimentation is expensive and often time consuming. Therefore, the development of novel computational method...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章


    authors: Manavalan B,Shin TH,Kim MO,Lee G

    更新日期:2018-03-27 00:00:00

  • Dysregulation of Mesenchymal Cell Survival Pathways in Severe Fibrotic Lung Disease: The Effect of Nintedanib Therapy.

    abstract::Impaired apoptotic clearance of myofibroblasts can result in the continuous expansion of scar tissue during the persistent injury in the lung. However, the molecular and cellular mechanisms underlying the apoptotic clearance of multiple mesenchymal cells including fibrocytes, fibroblasts and myofibroblasts in severe f...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章


    authors: Kasam RK,Reddy GB,Jegga AG,Madala SK

    更新日期:2019-05-17 00:00:00

  • Pharmacometabolomics Informs Viromics toward Precision Medicine.

    abstract::Nowadays, we are experiencing the big data era with the emerging challenge of single data interpretation. Although the advent of high-throughput technologies as well as chemo- and bio-informatics tools presents pan-omics data as the way forward to precision medicine, personalized health care and tailored-made therapeu...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章


    authors: Balasopoulou A,Patrinos GP,Katsila T

    更新日期:2016-10-27 00:00:00

  • Pharmacogenomic Diversity among Brazilians: Influence of Ancestry, Self-Reported Color, and Geographical Origin.

    abstract::BY VIRTUE OF BEING THE PRODUCT OF THE GENETIC ADMIXTURE OF THREE ANCESTRAL ROOTS: Europeans, Africans, and Amerindians, the present-day Brazilian population displays very high levels of genomic diversity, which have important pharmacogenetic/-genomic (PGx) implications. Recognition of this fact has prompted the creati...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章


    authors: Suarez-Kurtz G,Pena SD,Struchiner CJ,Hutz MH

    更新日期:2012-11-06 00:00:00

  • Computational Analysis of Therapeutic Neuroadaptation to Chronic Antidepressant in a Model of the Monoaminergic Neurotransmitter and Stress Hormone Systems.

    abstract::The clinical practice of selective serotonin reuptake inhibitor (SSRI) augmentation relies heavily on trial-and-error. Unfortunately, the drug combinations prescribed today fail to provide relief for many depressed patients. In order to identify potentially more effective treatments, we developed a computational model...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章


    authors: Camacho MB,Vijitbenjaronk WD,Anastasio TJ

    更新日期:2019-10-25 00:00:00

  • Leonurine Improves Age-Dependent Impaired Angiogenesis: Possible Involvement of Mitochondrial Function and HIF-1α Dependent VEGF Activation.

    abstract::Objective: Advanced age is associated with impaired angiogenesis in part because of mitochondrial dysfunction. We have recently reported that leonurine exerts protective effects in neuron via regulation of mitochondrial function. The aim of this study was to explore whether leonurine is able to attenuate mitochondrial...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章


    authors: Qi J,Wang JJ,Duan JL,Lu ZY,Yuan YG

    更新日期:2017-06-06 00:00:00

  • Layered Double Hydroxide Nanomaterials Encapsulating Angelica gigas Nakai Extract for Potential Anticancer Nanomedicine.

    abstract::We prepared hybrids consisting of Angelica gigas Nakai (AGN) root or flower extract and layered double hydroxide (LDH) for potential anticancer nanomedicine, as decursin species (DS) in AGN are known to have anticancer activity. Dimethylsulfoxide solvent was determined hybridization reaction media, as it has affinity ...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章


    authors: Kim HJ,Lee GJ,Choi AJ,Kim TH,Kim TI,Oh JM

    更新日期:2018-07-09 00:00:00

  • Conditioned Serum Enhances the Chondrogenic and Immunomodulatory Behavior of Mesenchymal Stem Cells.

    abstract::Osteoarthritis is one of the most common chronic health conditions associated with pain and disability. Advanced therapies based on mesenchymal stem cells have become valuable options for the treatment of these pathologies. Conditioned serum (CS, "Orthokine") has been used intra-articularly for osteoarthritic patients...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章


    authors: Blázquez R,Sánchez-Margallo FM,Reinecke J,Álvarez V,López E,Marinaro F,Casado JG

    更新日期:2019-06-28 00:00:00

  • Can Electronic Health Records Databases Complement Spontaneous Reporting System Databases? A Historical-Reconstruction of the Association of Rofecoxib and Acute Myocardial Infarction.

    abstract::Background: Several initiatives have assessed if mining electronic health records (EHRs) may accelerate the process of drug safety signal detection. In Europe, Exploring and Understanding Adverse Drug Reactions (EU-ADR) Project Focused on utilizing clinical data from EHRs of over 30 million patients from several Europ...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章


    authors: Patadia VK,Schuemie MJ,Coloma PM,Herings R,van der Lei J,Sturkenboom M,Trifirò G

    更新日期:2018-06-06 00:00:00