Apigenin, a chemopreventive bioflavonoid, induces AMP-activated protein kinase activation in human keratinocytes.

Abstract:

:AMP-activated protein kinase (AMPK) is a cellular energy sensor that is conserved in eukaryotes. Although AMPK is traditionally thought to play a major role in the regulation of cellular lipid and protein metabolism, recent discoveries reveal that AMPK inhibits mammalian target of rapamycin (mTOR) signaling and connects with several tumor suppressors such as liver kinase B1 (LKB1), p53, and tuberous sclerosis complex 2 (TSC2), indicating that AMPK may be a potential target for cancer prevention and treatment. For the first time, we demonstrated that apigenin, a naturally occurring nonmutagenic flavonoid, induced AMPK activation in human keratinocytes (both cultured HaCaT cell line and primary normal human epidermal keratinocytes). Through experiments with over-expression of constitutively active Akt and knockdown of LKB1 expression by siRNAs, we further found that the activation of AMPK by apigenin was not dependent on its inhibition of Akt, and was independent of the activation of upstream kinase LKB1. Instead, another upstream kinase of AMPK, calcium/calmodulin-dependent protein kinase kinase-β (CaMKKβ), was required for apigenin-induced AMPK activation. We have demonstrated that knockdown of CaMKKβ expression by siRNA or inhibition of CaMKKβ activity by either CaMKK inhibitor STO-609 or BAPTA-AM (1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester; a chelator of intracellular Ca(2+)) prevented apigenin-induced AMPK activation. Apigenin-induced AMPK activation inhibited mTOR signaling and further induced autophagy in human keratinocytes. These results suggest that one of the mechanisms by which apigenin exerts its chemopreventive action may be through activation of AMPK and induction of autophagy in human keratinocytes.

journal_name

Mol Carcinog

journal_title

Molecular carcinogenesis

authors

Tong X,Smith KA,Pelling JC

doi

10.1002/mc.20793

subject

Has Abstract

pub_date

2012-03-01 00:00:00

pages

268-79

issue

3

eissn

0899-1987

issn

1098-2744

journal_volume

51

pub_type

杂志文章
  • Mapping of tyrosine kinase gene family members in a Xiphophorus melanoma model.

    abstract::Xiphophorus fish have been the subject of intensive genetic research for more than 60 yr, primarily because of the availability of a number of interspecific hybrids that are malignant melanoma models with apparently simple oncogene and tumor suppressor gene determinants. The gene map of Xiphophorus is one of the most ...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/(sici)1098-2744(199807)22:3<150::aid-mc2>3

    authors: Morizot DC,McEntire BB,Della Coletta L,Kazianis S,Schartl M,Nairn RS

    更新日期:1998-07-01 00:00:00

  • Decreased expression of the adenomatous polyposis coli (Apc) and mutated in colorectal cancer (Mcc) genes in mouse lung neoplasia.

    abstract::A decrease in the intracellular concentrations of the transcripts for some tumor suppressor genes has been found during murine lung tumorigenesis; for p15INK4b and p16INK4a, this was due to homozygous deletions. We report here a decrease in the mRNA levels of the mutated in colorectal cancer (Mcc) and adenomatous poly...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:

    authors: Oreffo VI,Robinson S,You M,Wu MC,Malkinson AM

    更新日期:1998-01-01 00:00:00

  • Constitutive and phorbol-myristate-acetate regulated antioxidant defense of mouse epidermal JB6 cells.

    abstract::Because oxidative processes can participate in tumor promotion, it is likely that the cellular antioxidant defense also plays a role. We have compared the levels of the three major antioxidant enzymes, Cu,Zn-superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx), in promotable mouse epidermal JB6 cells ...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.2940020306

    authors: Crawford DR,Amstad PA,Foo DD,Cerutti PA

    更新日期:1989-01-01 00:00:00

  • 2-methoxyestradiol blocks cell-cycle progression at G(2)/M phase and inhibits growth of human prostate cancer cells.

    abstract::2-Methoxyestradiol (2-ME), an endogenous metabolite of 17beta-estradiol, is present in human blood and urine. Here we show for the first time that 2-ME significantly inhibited the growth of normal prostate epithelial cells and androgen-dependent LNCaP and androgen-independent DU145 prostate cancer cells. This growth i...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.1046

    authors: Kumar AP,Garcia GE,Slaga TJ

    更新日期:2001-07-01 00:00:00

  • Inhibition of oncogenic BRAF activity by indole-3-carbinol disrupts microphthalmia-associated transcription factor expression and arrests melanoma cell proliferation.

    abstract::Indole-3-carbinol (I3C), an anti-cancer phytochemical derived from cruciferous vegetables, strongly inhibited proliferation and down-regulated protein levels of the melanocyte master regulator micropthalmia-associated transcription factor (MITF-M) in oncogenic BRAF-V600E expressing melanoma cells in culture as well as...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.22472

    authors: Kundu A,Quirit JG,Khouri MG,Firestone GL

    更新日期:2017-01-01 00:00:00

  • Association of genetic variants of human telomerase with colorectal polyps and colorectal cancer risk.

    abstract::Human telomerase reverse transcriptase (TERT) gene encodes the catalytic subunit of telomerase and is located on chromosome 5p15, a genomic region which was found to be associated with multiple cancer types. But no associations with colorectal cancer (CRC) have been reported until recently. Therefore, the purpose of t...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.21911

    authors: Hofer P,Baierl A,Bernhart K,Leeb G,Mach K,Micksche M,Gsur A

    更新日期:2012-10-01 00:00:00

  • Magnolin targeting of ERK1/2 inhibits cell proliferation and colony growth by induction of cellular senescence in ovarian cancer cells.

    abstract::Ras/Raf/MEKs/ERKs and PI3 K/Akt/mTOR signaling pathways have key roles in cancer development and growth processes, as well as in cancer malignance and chemoresistance. In this study, we screened the therapeutic potential of magnolin using 15 human cancer cell lines and combined magnolin sensitivity with the CCLE mutao...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.22909

    authors: Song JH,Lee CJ,An HJ,Yoo SM,Kang HC,Lee JY,Kim KD,Kim DJ,Lee HS,Cho YY

    更新日期:2019-01-01 00:00:00

  • The polymorphisms and haplotypes of WWOX gene are associated with the risk of lung cancer in southern and eastern Chinese populations.

    abstract::The WW domain-containing oxidoreductase (WWOX) gene is an identified tumor suppressor gene, of which several single nucleotide polymorphisms have been reported to contribute to cancer susceptibility. We hypothesized that genetic variations in WWOX are associated with lung cancer risk. In two independent case-control s...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.21934

    authors: Huang D,Qiu F,Yang L,Li Y,Cheng M,Wang H,Ma G,Wang Y,Hu M,Ji W,Zhou Y,Lu J

    更新日期:2013-11-01 00:00:00

  • Transgenic insulin-like growth factor-1 stimulates activation of COX-2 signaling in mammary glands.

    abstract::Studies show that elevated insulin-like growth factor-1 (IGF-1) levels are associated with an increased risk of breast cancer; however, mechanisms through which IGF-1 promotes mammary tumorigenesis in vivo have not been fully elucidated. To assess the possible involvement of COX-2 signaling in the pro-tumorigenic effe...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.20868

    authors: Tian J,Lambertz I,Berton TR,Rundhaug JE,Kiguchi K,Shirley SH,Digiovanni J,Conti CJ,Fischer SM,Fuchs-Young R

    更新日期:2012-12-01 00:00:00

  • Genetic variants in the integrin gene predicted microRNA-binding sites were associated with the risk of prostate cancer.

    abstract::microRNAs (miRNA) silence target genes through Watson-Crick based binding to the 3'untranslated regions (3'UTR). Thus, polymorphisms in the miRNA-binding sites may disrupt this process and play a potential role in cancer pathogenesis. Integrins have been implicated in the genesis and development of many tumors. This s...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.21973

    authors: Liu J,Huang J,He Y,Liu J,Liao B,Liao G

    更新日期:2014-04-01 00:00:00

  • Association of expression quantitative trait loci for long noncoding RNAs with lung cancer risk in Asians.

    abstract::Identification of long noncoding RNA (lncRNA) expression quantitative trait loci (lncR-eQTL) that associated with lung cancer can provide insights into regulatory mechanisms of lncRNA, and help reveal the role of lncRNA in lung cancer. A two-stage case-control design was implemented in this study. We first selected th...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.23013

    authors: Sun Q,Wang Y,Fan J,Li Z,Zhang J,Wang L,Fan X,Ji M,Zhu M,Dai J,Ma H,Jin G,Hu Z,Shen H

    更新日期:2019-07-01 00:00:00

  • Aberrant transforming growth factor-beta signaling in azoxymethane-induced mouse colon tumors.

    abstract::Alterations in the transforming growth factor-beta (TGF-beta) pathway are implicated in the pathogenesis of colorectal cancer. We hypothesize that alterations in the TGF-beta pathway contribute to differential sensitivity of mice to the colon carcinogen azoxymethane (AOM). A/J (sensitive) and AKR/J (resistant) mice we...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.1055

    authors: Guda K,Giardina C,Nambiar P,Cui H,Rosenberg DW

    更新日期:2001-08-01 00:00:00

  • Induction of glutathione s-transferase-pi in Barrett's metaplasia and Barrett's adenocarcinoma cell lines.

    abstract::Barrett's metaplasia consists of columnar epithelium that replaces the normal esophageal mucosa in patients with chronic gastroesophageal reflux. Because intestinal-type Barrett's metaplasia is the major risk factor for adenocarcinoma development, understanding the mechanisms that predispose the esophageal mucosa to m...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/(sici)1098-2744(199902)24:2<128::aid-mc7>3

    authors: Compton KR,Orringer MB,Beer DG

    更新日期:1999-02-01 00:00:00

  • Protein phosphatase 2A is essential to maintain active Wnt signaling and its Aβ tumor suppressor subunit is not expressed in colon cancer cells.

    abstract::Canonical Wnt signaling is altered in most cases of colorectal cancer. Experimental evidence indicates that protein phosphatase 2A (PP2A) may play either positive or negative roles in Wnt signaling but its precise in vivo functions remain elusive. In this work, using colon cultured cell lines we showed that basal PP2A...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.22217

    authors: Carmen Figueroa-Aldariz M,Castañeda-Patlán MC,Santoyo-Ramos P,Zentella A,Robles-Flores M

    更新日期:2015-11-01 00:00:00

  • Dipyridamole intervention of breast cell carcinogenesis.

    abstract::Dietary prevention is a cost-efficient strategy to reduce the risk of human cancers. More than 85% breast cancers are sporadic and attributable to long-term exposure to environmental carcinogens through a multistep and multiyear disease process. We used our chronically induced cellular carcinogenesis model as a target...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.21970

    authors: Choudhary S,Sood S,Wang HC

    更新日期:2014-03-01 00:00:00

  • No involvement of Ki-ras or p53 gene mutations in colitis-associated rat colon tumors induced by 1-hydroxyanthraquinone and methylazoxymethanol acetate.

    abstract::1-Hydroxyanthraquinone (1-HA), which is present in some herbs, and methylazoxymethanol (MAM) acetate, a metabolite of azoxymethane, show synergistic carcinogenicity in rat colon, and 1-HA induces ulcerative changes with simultaneous severe inflammation of the entire colon. In this study, mutations in Ki-ras (exons 1 a...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.2940120403

    authors: Suzui M,Yoshimi N,Ushijima T,Hirose Y,Makita H,Wang A,Kawamori T,Tanaka T,Mori H,Nagao M

    更新日期:1995-04-01 00:00:00

  • Mutational specificity of 2-amino-3-methylimidazo-[4,5-f]quinoline in the hprt locus of CHO-K1 cells.

    abstract::2-Amino-3-methylimidazo[4,5-f]quinoline (IQ), a food carcinogen formed in cooked meats, can induce gene mutation at the hprt locus of CHO-K1 cells in the presence of hepatic S9 mix. To elucidate the molecular nature of IQ-induced mutation, we characterized the entire coding region of the hypoxanthine phosphoribosyl-tr...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.2940130209

    authors: Lee H,Shih MK

    更新日期:1995-06-01 00:00:00

  • Pre-existing Fas ligand (FasL) in cancer cells elicits tumor-specific protective immunity, but delayed induction of FasL expression after inoculation facilitates tumor formation.

    abstract::Overexpression of Fas ligand (FasL) in cancer cells elicits potential antitumor effects via recruitment of neutrophils. Conversely, FasL-expressing tumors may counterattack tumor-infiltrating lymphocytes by delivering apoptotic death signals via Fas/FasL interactions, which may lead to tumor escape. In order to distin...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.21909

    authors: Chiu HY,Sun GH,Chen SY,Wang HH,Ho MY,Chu CY,Wu WL,Jhou RS,Tsai YL,Huang RT,Sun KH,Tang SJ

    更新日期:2013-09-01 00:00:00

  • SOX6 represses tumor growth of clear cell renal cell carcinoma by HMG domain-dependent regulation of Wnt/β-catenin signaling.

    abstract::Sex-determining region Y box (SOXs) are expressed in various cells and control cell fate and differentiation in a multitude of physiologic processes. SOX6, a main representative of SOXs, is involved in the regulation of carcinogenesis in various human malignancies. However, the role of SOX6 in clear cell renal cell ca...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.23246

    authors: Chen L,Xie Y,Ma X,Zhang Y,Li X,Zhang F,Gao Y,Fan Y,Gu L,Wang L,Zhang X,Fu B

    更新日期:2020-10-01 00:00:00

  • The tumor suppressor parafibromin is required for posttranscriptional processing of histone mRNA.

    abstract::Parafibromin, encoded by the gene HRPT2, is a tumor suppressor protein associated with the RNA polymerase II-associated complex, Paf1 complex. HRPT2 mutations were first identified in patients with the multiple endocrine neoplasia syndrome, hyperparathyroidism-jaw tumor (HPT-JT) syndrome, and have also been found in s...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.20591

    authors: Farber LJ,Kort EJ,Wang P,Chen J,Teh BT

    更新日期:2010-03-01 00:00:00

  • The role of ERK2 in colorectal carcinogenesis is partly regulated by TRAPPC4.

    abstract::The extracellular signal-regulated kinase (ERK), mitogen-activated protein kinase (MAPK) pathway is an important cell proliferation pathway. We previously reported that the transport protein particle complex 4 (TRAPPC4), ERK2 interaction may activate ERK1/2, modulate pERK2 nuclear localization and regulate proliferati...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.22031

    authors: Weng YR,Kong X,Yu YN,Wang YC,Hong J,Zhao SL,Fang JY

    更新日期:2014-02-01 00:00:00

  • Further assessment of exome-wide UVR footprints in melanoma and their possible relevance.

    abstract::C>T substitutions at dipyrimidine sites dominate the melanoma genome. We recently analyzed the exomes of spontaneous and neonatal UVR-induced murine melanomas, noting a dramatic change in the genomic footprint at C>T substitutions in the latter. Here we re-analyzed published exome-wide footprints in human melanomas st...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.22623

    authors: Mukhopadhyay P,Roberts JA,Walker GJ

    更新日期:2017-06-01 00:00:00

  • Apple polyphenol phloretin potentiates the anticancer actions of paclitaxel through induction of apoptosis in human hep G2 cells.

    abstract::Phloretin (Ph), which can be obtained from apples, apple juice, and cider, is a known inhibitor of the type II glucose transporter (GLUT2). In this study, real-time PCR analysis of laser-capture microdissected (LCM) human hepatoma cells showed elevated expression (>5-fold) of GLUT2 mRNA in comparison with nonmalignant...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.20480

    authors: Yang KC,Tsai CY,Wang YJ,Wei PL,Lee CH,Chen JH,Wu CH,Ho YS

    更新日期:2009-05-01 00:00:00

  • KIT polymorphisms were associated with the risk for head and neck squamous carcinoma in Chinese population.

    abstract::KITLG/KIT pathway plays a vital role in multiple types of human cancer including head and neck squamous cell carcinoma (HNSCC). Genetic variations in KITLG and KIT may affect the expression or function of these genes, thereby modifying cancer risk. In this study, we evaluated the association of KITLG and KIT polymorph...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.22487

    authors: Hang D,Yuan H,Liu L,Wang L,Miao L,Zhu M,Du J,Dai J,Hu Z,Chen N,Shen H,Ma H

    更新日期:2017-01-01 00:00:00

  • Melatonin modulated autophagy and Nrf2 signaling pathways in mice with colitis-associated colon carcinogenesis.

    abstract:UNLABELLED:Colon carcinogenesis is long known to be associated with ulcerative colitis (UC), a chronic gastrointestinal disorder. Various pre-clinical and clinical studies have shown that melatonin (MEL) has beneficial effects in cancer. However, elucidation of the detailed molecular mechanisms involved in MEL-mediated...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.22274

    authors: Trivedi PP,Jena GB,Tikoo KB,Kumar V

    更新日期:2016-03-01 00:00:00

  • Discordant effects of activator protein-1 transcription factor on gene regulation, invasion, and metastasis in spontaneous, radiation-induced, and fos-induced osteosarcomas.

    abstract::Bone cells are a prime target for the biological function of the fos/jun (activating protein-1 (AP-1)) transcription factor complex. Deregulated expression of c-fos or v-fos in bone cells induces tumorigenicity and the formation of non-metastatic osteosarcomas. In contrast, fos oncogenes transform fibroblasts to an in...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:

    authors: Rupp B,Lorenz U,Schmidt J,Werenskiold AK

    更新日期:1998-10-01 00:00:00

  • Energy balance modulates colon tumor growth: Interactive roles of insulin and estrogen.

    abstract::Obesity increases colorectal cancer (CRC) risk and progression. However, the impact of obesity on CRC in women is dependent on ovarian hormone status. The purpose of this study was to determine the interactive roles of obesity and ovarian hormones on serum markers of inflammation, cell signaling, and transplanted colo...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.20720

    authors: Rondini EA,Harvey AE,Steibel JP,Hursting SD,Fenton JI

    更新日期:2011-05-01 00:00:00

  • c-Fos accelerates hepatocyte conversion to a fibroblastoid phenotype through ERK-mediated upregulation of paxillin-Serine178 phosphorylation.

    abstract::Transforming growth factor beta (TGF-beta) exerts an important role in the late steps of carcinogenesis by cooperating with Ras to induce cell motility and tumor invasion. The transcription complex AP-1 has been implicated in the regulation of genes involved in motility and invasion, by mechanisms not yet delineated. ...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.20492

    authors: Güller MC,André J,Legrand A,Setterblad N,Mauviel A,Verrecchia F,Daniel F,Bernuau D

    更新日期:2009-06-01 00:00:00

  • Ki-ras activation and expression in transformed mouse lung cell lines.

    abstract::The Ki-ras proto-oncogene is activated by specific point mutations and is the transforming gene often identified in rodent and human lung tumors. An in vitro model to aid in the study of the consequences of Ki-ras activation and expression in mouse lung is needed. Accordingly, we have examined cell lines derived from ...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.2940030508

    authors: Pan YH,Nuzum EO,Hanson LA,Beer DG

    更新日期:1990-01-01 00:00:00

  • Phase II enzyme inducer, sulforaphane, inhibits UVB-induced AP-1 activation in human keratinocytes by a novel mechanism.

    abstract::Ultraviolet (UV) light-induced activation of activator protein-1 (AP-1), resulting at least in part from oxidative stress, promotes skin carcinogenesis. It has not yet been determined whether elevating cellular phase II enzymes and glutathione (GSH) levels inhibits the AP-1 activation. We have, therefore, examined the...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.20052

    authors: Zhu M,Zhang Y,Cooper S,Sikorski E,Rohwer J,Bowden GT

    更新日期:2004-11-01 00:00:00