Esculetin inhibits cell proliferation through the Ras/ERK1/2 pathway in human colon cancer cells.

Abstract:

:Esculetin, a phenolic compound, has been shown to inhibit the growth of colon tumors in animal studies. However, the roles of signaling pathways and cell cycle regulation in the esculetin-induced inhibition of cancer cell growth, remain to be elucidated. The present study suggests a novel mechanism for the Ras/ERK1/2 pathway in esculetin-treated human colon cancer HCT116 cells. The treatment of cells with esculetin resulted in significant growth inhibition and G1 phase cell cycle arrest, which led to the down-regulation of cyclin and cyclin-dependent kinase (CDK) expressions. This G1 phase cell cycle arrest was associated with the up-regulation of p27KIP expression. In addition, ERK1/2 was activated by esculetin. The pre-treatment of cells with the MEK1/2-specific inhibitor, PD98059, blocked the p27KIP expression induced by esculetin. Blockage of the ERK1/2 function consistently prevented the inhibition of cell proliferation and decreased G1 phase cell cycle protein levels. Furthermore, Ras activation was increased by the esculetin treatment. Transient transfection of the dominant negative Ras (RasN17) mutant gene abolished both the ERK1/2 activity and p27KIP expression induced by esculetin. Finally, the overexpression of RasN17 suppressed the esculetin-induced reduction in cell proliferation and cell cycle proteins. In conclusion, these results indicate that the Ras/ERK1/2 pathway is mediated by the p27KIP1 induction, leading to a reduction in cyclin/CDK complexes in the esculetin-induced inhibition of colon cancer cell growth. Overall, these findings indicate that the molecular action of esculetin has therapeutic potential for the treatment of colon malignancies.

journal_name

Oncol Rep

journal_title

Oncology reports

authors

Park SS,Park SK,Lim JH,Choi YH,Kim WJ,Moon SK

subject

Has Abstract

pub_date

2011-01-01 00:00:00

pages

223-30

issue

1

eissn

1021-335X

issn

1791-2431

journal_volume

25

pub_type

杂志文章
  • Miconazole induces apoptosis via the death receptor 5-dependent and mitochondrial-mediated pathways in human bladder cancer cells.

    abstract::Miconazole (MIC), an antifungal agent, diplays anti‑tumorigenic activity in various types of human cancers, including bladder cancer, yet its mechanism of antitumor action is not well understood. In the present study, we demonstrated that, in a cell viability assay, MIC had a cytotoxic effect on human T24, J82 and TSG...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2017.5608

    authors: Yuan SY,Shiau MY,Ou YC,Huang YC,Chen CC,Cheng CL,Chiu KY,Wang SS,Tsai KJ

    更新日期:2017-06-01 00:00:00

  • GnRH agonists and antagonists decrease the metastatic progression of human prostate cancer cell lines by inhibiting the plasminogen activator system.

    abstract::Prostate cancer (PCa) growth initially depends on circulating androgens. Gonadotropin-releasing hormone (GnRH) agonists are currently used for the treatment of PCa. However, after an initial responsiveness to hormonal deprivation, PCa progresses and metastasizes. Recently, also GnRH antagonists have been used for clin...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.15.2.393

    authors: Dondi D,Festuccia C,Piccolella M,Bologna M,Motta M

    更新日期:2006-02-01 00:00:00

  • Peroxiredoxin 1 is a tumor-associated antigen in esophageal squamous cell carcinoma.

    abstract::Peroxiredoxin 1 (Prdx1) is an antioxidant and plays an important role in H2O2-mediated cell signaling. We previously found that the expression level of Prdx1 was elevated in esophagus squamous cell carcinoma (ESCC) tissue using a proteomics approach. Since overexpressed protein can induce an autoimmune response, to fu...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2013.2714

    authors: Ren P,Ye H,Dai L,Liu M,Liu X,Chai Y,Shao Q,Li Y,Lei N,Peng B,Yao W,Zhang J

    更新日期:2013-11-01 00:00:00

  • Overexpression of IL-9 induced by STAT3 phosphorylation is mediated by miR-155 and miR-21 in chronic lymphocytic leukemia.

    abstract::Interleukin‑9 (IL‑9) can function as both a positive and negative regulator of immune response, however the role of IL‑9 in tumor immunity is poorly understood. Chronic lymphocytic leukemia (CLL) is the most common chronic lympho‑proliferative disorder. Twenty CLL patients from 2010 to 2011 were recruited in the study...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2018.6367

    authors: Chen N,Feng L,Qu H,Lu K,Li P,Lv X,Wang X

    更新日期:2018-06-01 00:00:00

  • Trop2 is a potential biomarker for the promotion of EMT in human breast cancer.

    abstract::Trop2 is considered to have an important function in tumor metastasis and the promotion of epithelial‑mesenchymal transition (EMT). E‑cadherin is a crucial factor in intercellular adhesion and EMT transformation. In the present study, we detected the expression of Trop2 and E‑cadherin in breast cancer (BC) to better d...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2018.6496

    authors: Zhao W,Kuai X,Zhou X,Jia L,Wang J,Yang X,Tian Z,Wang X,Lv Q,Wang B,Zhao Y,Huang W

    更新日期:2018-08-01 00:00:00

  • Suppression of VEGF expression through interruption of the HIF‑1α and Akt signaling cascade modulates the anti‑angiogenic activity of DAPK in ovarian carcinoma cells.

    abstract::Death-associated protein kinase (DAPK) plays an important role in apoptosis regulation and has been shown to maintain antitumor and metastasis suppressor properties. In the present study, we investigated whether DAPK overexpression may mediate vascular endothelial growth factor (VEGF)/hypoxia-inducible factor-1α (HIF-...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2013.2928

    authors: Park ST,Kim BR,Park SH,Lee JH,Lee EJ,Lee SH,Rho SB

    更新日期:2014-02-01 00:00:00

  • Triptolide induced DNA damage in A375.S2 human malignant melanoma cells is mediated via reduction of DNA repair genes.

    abstract::Numerous studies have demonstrated that triptolide induces cell cycle arrest and apoptosis in human cancer cell lines. However, triptolide-induced DNA damage and inhibition of DNA repair gene expression in human skin cancer cells has not previously been reported. We sought the effects of triptolide on DNA damage and a...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2012.2170

    authors: Chueh FS,Chen YL,Hsu SC,Yang JS,Hsueh SC,Ji BC,Lu HF,Chung JG

    更新日期:2013-02-01 00:00:00

  • Reactive oxygen species promote ovarian cancer progression via the HIF-1α/LOX/E-cadherin pathway.

    abstract::Reactive oxygen species (ROS) can drive the de‑differentiation of tumor cells leading to the process of epithelial-to-mesenchymal transition (EMT) to enhance invasion and metastasis. The invasive and metastatic phenotype of malignant cells is often linked to loss of E-cadherin expression, a hallmark of EMT. Recent stu...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2014.3448

    authors: Wang Y,Ma J,Shen H,Wang C,Sun Y,Howell SB,Lin X

    更新日期:2014-11-01 00:00:00

  • Comprehensive analysis of a novel lncRNA profile reveals potential prognostic biomarkers in clear cell renal cell carcinoma.

    abstract::Clear cell renal cell carcinoma (ccRCC) is the main subtype of malignant kidney cancer. Long non‑coding RNA (lncRNA) serves a key role in predicting survival in patients with cancer. The present study aimed to develop an lncRNA‑related signature of prognostic values for patients with ccRCC. RNA sequencing data of 454 ...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2018.6540

    authors: Liu T,Sui J,Zhang Y,Zhang XM,Wu WJ,Yang S,Xu SY,Hong WW,Peng H,Yin LH,Pu YP,Liang GY

    更新日期:2018-09-01 00:00:00

  • In vivo evidence for a significant role of folylpolyglutamate synthase in combined chemotherapy with oral fluoropyrimidine, UFT or S-1, and leucovorin.

    abstract::Combined chemotherapy with 5-fluorouracil and leucovorin (LV) has been widely used for the treatment of patients with colorectal cancer. Given that LV effects are attributable to increased levels of reduced folate in cancer cells, we attempted here to show the in vivo role of folylpolyglutamate synthetase (FPGS), whic...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2011.1206

    authors: Tsukioka S,Sakamoto E,Tsujimoto H,Nakagawa F,Saito H,Uchida J,Kiniwa M,Fukushima M

    更新日期:2011-05-01 00:00:00

  • GL15 and U251 glioblastoma-derived human cell lines are peculiarly susceptible to induction of mitotic death by very low concentrations of okadaic acid.

    abstract::The challenging possibility of selectively inducing mitotic death in tumor cells by combining genotoxic agents with the inhibition of G2 checkpoints of the cell cycle is the subject of intensive investigation. We show that very low concentrations (3.5 and 5 nM) of okadaic acid induce mitotic death in two glioblastoma ...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Castigli E,Sciaccaluga M,Schiavoni G,Brozzi F,Fabiani R,Gorello P,Gianfranceschi GL

    更新日期:2006-02-01 00:00:00

  • DNA damage sensor protein hRad9, a novel molecular target for lung cancer treatment.

    abstract::DNA damage sensor proteins are recognized as upstream components of the DNA damage checkpoint signaling pathway and are required for cell cycle control and the induction of apoptosis. hRad9 plays an important role as an upstream regulator of checkpoint signaling. In our previous studies, we confirmed the significant a...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Yuki T,Maniwa Y,Doi T,Okada K,Nishio W,Hayashi Y,Okita Y

    更新日期:2008-11-01 00:00:00

  • Molecular characterization as a target for cancer therapy in relation to orphan status disorders (Review).

    abstract::The long-term effort in investigating chemical methods to eliminate only cancer cells has improved our knowledge and has led to the development of new drugs. The targets for cancer treatment may be large polymeric molecules such as DNA or microtubules as well as regulatory pathways for tumor development and cell survi...

    journal_title:Oncology reports

    pub_type: 杂志文章,评审

    doi:10.3892/or.9.6.1257

    authors: Stathopoulos GP

    更新日期:2002-11-01 00:00:00

  • Cellular processing in the SW1222 cell line of mAb A33 directly and indirectly radiohalogenated.

    abstract::Investigations into the cellular processing of radiolabeled monoclonal antibodies (mAbs) for their further use in radioimmunodiagnosis and cancer therapy are needed in order to understand the fate of internalized and catabolized mAbs. The anti-colorectal cancer mAb, A33, was labelled with 76Br and 125I using the direc...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Höglund J,Orlova A,Sundin A,Lundqvist H,Tolmachev V

    更新日期:2006-07-01 00:00:00

  • Loss of p21WAF1/CIP1 expression in invasive fronts of oral tongue squamous cell carcinomas is correlated with tumor progression and poor prognosis.

    abstract::The clinicopathological significance of cell-cycle proteins has remained unclear in oral tongue squamous cell carcinomas (OTSCC). In the current study, we evaluated several cell-cycle proteins in relation to clinicopathological parameters and disease outcome for OTSCC. A total of 123 previously untreated patients with...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Goto M,Tsukamoto T,Inada K,Mizoshita T,Ogawa T,Terada A,Hyodo I,Shimozato K,Hasegawa Y,Tatematsu M

    更新日期:2005-10-01 00:00:00

  • The Das-1 immunostain is useful for discriminating metastatic colon adenocarcinoma from cholangiocarcinoma and hepatocellular carcinoma.

    abstract::The distinction between cholangiocarcinoma, hepatocellular carcinoma and liver metastasis is important but at times difficult solely on microscopic appearances. The Das-1 immunostain exhibits specificity for colonic epithelium. However, its staining of cholangiocarcinomas and hepatocellular carcinomas has not been ext...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Zimmerman RL,Das KM,Fogt F,Burke M,Murakata LA

    更新日期:2002-11-01 00:00:00

  • Expansion of quiescent lung adenocarcinoma CD8+ T cells by MUC1-8-mer peptide-T2 cell-β2 microglobulin complexes.

    abstract::Adoptive immunotherapy requires the isolation of CD8+ T cells specific for tumor-associated antigens, their expansion in vitro and their transfusion to the patient to mediate a therapeutic effect. MUC1 is an important adenocarcinoma antigen immunogenic for T cells. The MUC1-derived SAPDTRPA (MUC1-8-mer) peptide is a p...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2015.4328

    authors: Atzin-Méndez JA,López-González JS,Báez R,Arenas-Del Angel MC,Montaño LF,Silva-Adaya D,Lascurain R,Gorocica P

    更新日期:2016-01-01 00:00:00

  • Expression of angiogenic markers in the peripheral blood of docetaxel-treated advanced breast cancer patients: a Hellenic Cooperative Oncology Group (HeCOG) study.

    abstract::It is well known that low-dose metronomic chemotherapy has antiangiogenic activity. The aim of the present trial was to investigate the antiangiogenic properties of weekly docetaxel in patients with metastatic breast cancer. In total, 157 metastatic breast cancer patients received 3...

    journal_title:Oncology reports

    pub_type: 临床试验,杂志文章

    doi:10.3892/or.2011.1504

    authors: Pectasides D,Papaxoinis G,Kotoula V,Fountzilas H,Korantzis I,Koutras A,Dimopoulos AM,Papakostas P,Aravantinos G,Varthalitis I,Kosmidis P,Skarlos D,Bournakis E,Bafaloukos D,Kalofonos HP,Kalogeras KT,Fountzilas G

    更新日期:2012-01-01 00:00:00

  • MicroRNA-605 functions as a tumor suppressor by targeting INPP4B in melanoma.

    abstract::MicroRNAs (miRNAs) play crucial roles in the initiation and progression of various cancers, including melanoma. Recently, the genetic variants and deregulation of miR-605 have been reported to participate in carcinogenesis. However, the expression status of the miR-605 in melanoma tissues and its role in melanoma prog...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2017.5740

    authors: Chen L,Cao Y,Rong D,Wang Y,Cao Y

    更新日期:2017-08-01 00:00:00

  • Paclitaxel enhances tumoricidal potential of TRAIL via inhibition of MAPK in resistant gastric cancer cells.

    abstract::Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) holds promise for cancer therapy due to its unique capacity to selectively trigger apoptosis in cancer cells. However, TRAIL therapy is greatly hampered by its resistance. A preclinical successful strategy is to identify combination treatments that sensit...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2016.4666

    authors: Li L,Wen XZ,Bu ZD,Cheng XJ,Xing XF,Wang XH,Zhang LH,Guo T,Du H,Hu Y,Fan B,Ji JF

    更新日期:2016-05-01 00:00:00

  • Genome-wide DNA methylation analysis in hepatocellular carcinoma.

    abstract::Epigenetic changes as well as genetic changes are mechanisms of tumorigenesis. We aimed to identify novel genes that are silenced by DNA hypermethylation in hepatocellular carcinoma (HCC). We screened for genes with promoter DNA hypermethylation using a genome-wide methylation microarray analysis in primary HCC (the d...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2016.4619

    authors: Yamada N,Yasui K,Dohi O,Gen Y,Tomie A,Kitaichi T,Iwai N,Mitsuyoshi H,Sumida Y,Moriguchi M,Yamaguchi K,Nishikawa T,Umemura A,Naito Y,Tanaka S,Arii S,Itoh Y

    更新日期:2016-04-01 00:00:00

  • Combined effects of atorvastatin and aspirin on growth and apoptosis in human prostate cancer cells.

    abstract::Epidemiologic studies indicate the use of either statins or aspirin have beneficial effects in prostate cancer patients. The present study was undertaken to evaluate the effects and mechanisms of atorvastatin and aspirin alone or in combination in human prostate cancer cells cultured in vitro and grown as xenograft tu...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2017.5353

    authors: He Y,Huang H,Farischon C,Li D,Du Z,Zhang K,Zheng X,Goodin S

    更新日期:2017-02-01 00:00:00

  • Ultrasound-targeted microbubble destruction-mediated downregulation of CD133 inhibits epithelial-mesenchymal transition, stemness and migratory ability of liver cancer stem cells.

    abstract::Hepatocellular carcinoma (HCC) is an aggressive disease with a poor outcome due to the high incidence of metastasis. Cancer stem cells (CSCs) have been identified to be responsible for tumor progression and may be generated by epithelial-mesenchymal transition (EMT) characteristics. CD133 is a specific surface marker ...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2015.4270

    authors: Liu YM,Li XF,Liu H,Wu XL

    更新日期:2015-12-01 00:00:00

  • Loss of ONECUT1 expression in human pancreatic cancer cells.

    abstract::ONECUT1 (HNF-6) is the prototype of a new class of homeodomain transcription factors, that controls the development of pancreatic ducts during mouse development. In the present study, the role of ONECUT1 and its targeted genes TCF2, PKHD1 and CYS1 was analyzed in human pancreatic ductal adenocarcinoma (PDAC). mRNA lev...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Jiang X,Zhang W,Kayed H,Zheng P,Giese NA,Friess H,Kleeff J

    更新日期:2008-01-01 00:00:00

  • [Corrigendum] Ski prevents TGF‑β‑induced EMT and cell invasion by repressing SMAD‑dependent signaling in non‑small cell lung cancer.

    abstract::Following the publication of the above paper, an interested reader drew to our attention apparent anomalies associated with Figs. 2, 3 and 4; essentially, these three figures contained panels exhibiting overlapping data, such that data purportedly relating to different experiments were apparently drawn from the same o...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2020.7868

    authors: Yang H,Zhan L,Yang T,Wang L,Li C,Zhao J,Lei Z,Li X,Zhang HT

    更新日期:2020-11-25 00:00:00

  • Silencing MARCH1 suppresses proliferation, migration and invasion of ovarian cancer SKOV3 cells via downregulation of NF-κB and Wnt/β-catenin pathways.

    abstract::Membrane-associated RING-CH (MARCH) belongs to the family of RING-CH type E3 ubiquitin ligases. MARCH1 ubiquitinates and downregulates MHC class II expression in APCs and targets major players of the immune system. However, the role of MARCH1 in ovarian cancer has not been elucidated. The present study investigated th...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2016.5076

    authors: Meng Y,Hu J,Chen Y,Yu T,Hu L

    更新日期:2016-11-01 00:00:00

  • Restoration of miR-7 expression suppresses the growth of Lewis lung cancer cells by modulating epidermal growth factor receptor signaling.

    abstract::microRNAs are an abundant class of short endogenous non-coding RNAs that function as important regulators of multiple target genes and participate in diverse biological roles in carcinogenesis. However, the role of miR-7 in lung cancer remains unclear and requires further elucidation. In the present study, we found a ...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2014.3519

    authors: Li J,Zheng Y,Sun G,Xiong S

    更新日期:2014-12-01 00:00:00

  • Antitumor and antiangiogenic activity of soy isoflavone genistein in mouse models of melanoma and breast cancer.

    abstract::Tumor invasion, angiogenesis and metastasis involve secretion of proteolytic enzymes and cell migration into blood vessels. Tumor cells are capable of degrading the extracellular matrix via a proteolytic cascade that includes urokinase-type plasminogen activator (uPA) and matrix metalloproteases (MMPs). We have invest...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Farina HG,Pomies M,Alonso DF,Gomez DE

    更新日期:2006-10-01 00:00:00

  • Casticin induces growth suppression and cell cycle arrest through activation of FOXO3a in hepatocellular carcinoma.

    abstract::Casticin, a polymethoxyflavone, has been reported to exert anticancer activities. The objectives of this study were to examine the molecular mechanisms by which casticin induces the growth inhibition and cell cycle arrest in human hepatocellular carcinoma (HCC) cells. The HCC cell l...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2012.2076

    authors: He L,Yang X,Cao X,Liu F,Quan M,Cao J

    更新日期:2013-01-01 00:00:00

  • TIPE2 inhibits GC via regulation of cell proliferation, apoptosis and inflammation.

    abstract::Gastric cancer (GC), a type of gastric mucosal epithelium disease caused by common malignant tumors, has become a major threat to human health and survival. Tumor necrosis factor‑α‑induced protein‑8 like‑2 (TIPE2) is a negative immune regulatory factor that is selectively expressed in immune organs, immune cells and v...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2018.6576

    authors: Lin Z,Liu W,Xiao C,Fan Y,Zhuang G,Qi Z

    更新日期:2018-09-01 00:00:00