Hispidulin suppresses tumor growth and metastasis in renal cell carcinoma by modulating ceramide-sphingosine 1-phosphate rheostat.

Abstract:

:Sphingosine 1-phosphate (S1P) rheostat is considered as a key signal that determines cell fate. This study aimed to report that hispidulin, a polyphenolic flavonoid, exerted anti-growth and anti-metastasis effects against renal cell carcinoma (RCC) by modulating the balance of ceramide-S1P. In vitro studies showed that hispidulin could effectively inhibit cell proliferation, cell migration, cell invasion, and epithelial-mesenchymal transition, and promote cell apoptosis in Caki-2 and A498 cell lines. Moreover, it also increased the ceramide/S1P ratio. Consistent with the in vitro findings, the efficacy of hispidulin in vivo showed that it effectively suppressed tumor growth and lung metastasis. Furthermore, the results revealed that hispidulin significantly suppressed the activity of sphingosine kinase 1 (Sphk1) in RCC cells; however, no significant change was observed in the mRNA or protein expression of Sphk1. The overexpression of Sphk1 could significantly abrogate the anti-growth and anti-metastasis effects of hispidulin, whereas the siRNA-targeting Sphk1 or Sphk1 inhibitor was able to augment the anticancer effects of hispidulin against RCC. Moreover, hispidulin interfered with the phosphorylation and translocation of Sphk1, leading to inhibitory effects of Sphk1 activity. In summary, the findings suggested that hispidulin suppressed tumor growth and metastasis by inhibiting the Sphk1 activity and consequently modulating ceramide-S1P rheostat. It also presented a new explanation for the antitumor mechanisms of hispidulin against RCC.

journal_name

Am J Cancer Res

authors

Gao MQ,Gao H,Han M,Liu KL,Peng JJ,Han YT

subject

Has Abstract

pub_date

2017-07-01 00:00:00

pages

1501-1514

issue

7

issn

2156-6976

journal_volume

7

pub_type

杂志文章,收录出版
  • Aberrant miR-1246 expression promotes radioresistance in non-small cell lung cancer: a potential prognostic biomarker and radiotherapy sensitization target.

    abstract::Radiosensitivity varies among patients with non-small cell lung cancer (NSCLC). In this work, we aimed to investigate microRNAs associated with this heterogeneity among individuals. We selected miR-1246 from the microRNAs that were revealed by microarray experiments to be differentially expressed between radioresistan...

    journal_title:American journal of cancer research

    pub_type: 杂志文章,收录出版

    doi:

    authors: Fan L,Wang J,Cao Q,Ding X,Li B

    更新日期:2020-01-01 00:00:00

  • Docosahexaenoic acid (DHA), an omega-3 fatty acid, inhibits tumor growth and metastatic potential of ovarian cancer.

    abstract::Omega-3 polyunsaturated fatty acids (PUFAs), such as those found in fish oil, are thought to have anti-tumorigenic effects and may help to treat and prevent cancer, including ovarian cancer. Thus, we aimed to evaluate the potential of docosahexaenoic acid (DHA), an omega-3 PUFA, as a therapeutic agent in ovarian cance...

    journal_title:American journal of cancer research

    pub_type: 杂志文章

    doi:

    authors: West L,Yin Y,Pierce SR,Fang Z,Fan Y,Sun W,Tucker K,Staley A,Zhou C,Bae-Jump V

    更新日期:2020-12-01 00:00:00

  • High visfatin expression predicts poor prognosis of upper tract urothelial carcinoma patients.

    abstract::Visfatin, a newly discovered adipocytokine, is a pro-inflammatory cytokine. This study aimed to evaluate the predictive value of visfatin on prognosis of patients with upper tract urothelial carcinoma. One-hundred and five patients (median age=64, range=24-84 years) were included in this study. Visfatin expression in ...

    journal_title:American journal of cancer research

    pub_type: 杂志文章

    doi:

    authors: Ke HL,Lin HH,Li WM,Li CC,Chang LL,Lee YC,Huang CN,Wu WJ

    更新日期:2015-07-15 00:00:00

  • MicroRNA-122 inhibits proliferation and invasion in gastric cancer by targeting CREB1.

    abstract::MicroRNA-122 (miR-122) has been implicated in tumor development and progression in various types of cancers. However, the biological function and regulatory mechanisms of miR-122 in gastric cancer (GC) remain largely unknown. We aimed to determine the biological role and underlying mechanism of miR-122 in GC. Real tim...

    journal_title:American journal of cancer research

    pub_type: 杂志文章

    doi:

    authors: Rao M,Zhu Y,Zhou Y,Cong X,Feng L

    更新日期:2017-02-01 00:00:00

  • Clinicopathological significance of Fas and Fas ligand expressions in esophageal cancer [Retraction].

    abstract::[This retracts the article on p. 2865 in vol. 5, PMID: 26609492.]. ...

    journal_title:American journal of cancer research

    pub_type: 撤回出版物

    doi:

    authors:

    更新日期:2015-12-15 00:00:00

  • Six1 promotes glioblastoma cell proliferation and invasion by upregulation of connective tissue growth factor.

    abstract::Glioblastoma multiforme (GBM) is the deadliest and most common form of malignant primary brain tumor in humans. However, until now, little is known about the glioma genesis and progression at the molecular level. Here we report that overexpression of sine oculis homeobox homolog 1 (Six1), a developmental transcription...

    journal_title:American journal of cancer research

    pub_type: 杂志文章

    doi:

    authors: Tian T,Li A,Lu H,Luo R,Zhang M,Li Z

    更新日期:2015-04-15 00:00:00

  • MiR-26a inhibits thyroid cancer cell proliferation by targeting ARPP19.

    abstract::miRNA, which involves in pathogenesis of thyroid cancer via different targets, has been found aberrantly expressed in thyroid cancer. Modes of actions of miR-26a in papillary thyroid carcinoma (PTC), however, have not been fully understood to this date. In vitro results obtained from this research confirmed miR-26a wa...

    journal_title:American journal of cancer research

    pub_type: 杂志文章

    doi:

    authors: Gong Y,Wu W,Zou X,Liu F,Wei T,Zhu J

    更新日期:2018-06-01 00:00:00

  • Disruption of the menin-MLL interaction triggers menin protein degradation via ubiquitin-proteasome pathway.

    abstract::Menin, a protein encoded by the MEN1 gene, suppresses cancers associated with multiple endocrine neoplasia type 1 (MEN1), but promotes the development of a subset of leukemia induced by mixed lineage leukemia (MLL)-derived fusion proteins (MLL-FPs). The crystal structure of menin indicates that it acts as a scaffold p...

    journal_title:American journal of cancer research

    pub_type: 杂志文章

    doi:

    authors: Wu Y,Doepner M,Hojnacki T,Feng Z,Katona BW,He X,Ma J,Cao Y,Busino L,Zhou F,Hua X

    更新日期:2019-08-01 00:00:00

  • Interferon regulatory factor-1 suppresses DNA damage response and reverses chemotherapy resistance by downregulating the expression of RAD51 in gastric cancer.

    abstract::Recent studies have shown that IRF-1 plays a significant role in various tumour-induced chemoresistance, but its role and mechanism in gastric cancer-associated chemoresistance are not clear. Our study showed that IRF-1 expression could reverse gastric cancer-related chemoresistance. Dysregulated DNA repair is an impo...

    journal_title:American journal of cancer research

    pub_type: 杂志文章

    doi:

    authors: Tan L,Yuan J,Zhu W,Tao K,Wang G,Gao J

    更新日期:2020-04-01 00:00:00

  • Verteporfin inhibits YAP function through up-regulating 14-3-3σ sequestering YAP in the cytoplasm.

    abstract::Yes-associated protein (YAP), the central mediator of Hippo pathway, not only regulates a diversity of cellular processes during development but also plays a pivotal role in tumorigenesis. YAP is overexpressed in many types of human cancers with its expression level being associated with patient outcomes. Thus, inhibi...

    journal_title:American journal of cancer research

    pub_type: 杂志文章

    doi:

    authors: Wang C,Zhu X,Feng W,Yu Y,Jeong K,Guo W,Lu Y,Mills GB

    更新日期:2015-12-15 00:00:00

  • Nanoparticle-mediated down-regulation of TWIST increases radiosensitivity of nasopharyngeal carcinoma cells via ERK pathway.

    abstract::Evidence suggests that over-expression of TWIST, an epithelial-mesenchymal transition inducer, might have a correlation with cancer progression and chemoresistance. However, its roles in radioresistance of cancer have rarely been reported. High TWIST expression was detected in nasopharyngeal carcinoma (NPC) and associ...

    journal_title:American journal of cancer research

    pub_type: 杂志文章

    doi:

    authors: Zhuo X,Chang A,Huang C,Yang L,Zhao H,Wu Y,Zhou Q

    更新日期:2015-03-15 00:00:00

  • KRas-LCS6 polymorphism does not impact on outcomes in ovarian cancer.

    abstract::Epithelial ovarian cancer is a malignancy with high rate of death due to an advanced disease at diagnosis and frequent relapse after chemotherapy. Nowadays, there is a lack of knowledge for clear risk factors and predictive and/or prognostic genetic markers although genomic alterations such as mutations in p53, PTEN, ...

    journal_title:American journal of cancer research

    pub_type: 杂志文章

    doi:

    authors: Caiola E,Rulli E,Fruscio R,Buda A,Broggini M,Marabese M

    更新日期:2012-01-01 00:00:00

  • Induction of cells with prostate cancer stem-like properties from mouse induced pluripotent stem cells via conditioned medium.

    abstract::Cancer stem cells (CSCs) that closely correlated with tumor growth, metastasis, provide a plausible explanation for chemoresistance and cancer relapse. CSCs are usually isolated and enriched from carcinoma cells, which is inconvenient, low-efficient, and even unreliable. Here, we converted mouse induced pluripotent st...

    journal_title:American journal of cancer research

    pub_type: 杂志文章

    doi:

    authors: Xu N,Li X,Watanabe M,Ueki H,Hu H,Li N,Araki M,Wada K,Xu A,Liu C,Nasu Y,Huang P

    更新日期:2018-08-01 00:00:00

  • Humanized mouse model: a review on preclinical applications for cancer immunotherapy.

    abstract::Due to the refractory and partial sensitive treatments to malignant cancers, immunotherapy has increasingly become a hotspot in effective anti-tumor research. However, at present, existing animal models could not accurately describe the interaction between human tissue and tumor cells for preclinical trials. Furthermo...

    journal_title:American journal of cancer research

    pub_type: 杂志文章,评审

    doi:

    authors: Yin L,Wang XJ,Chen DX,Liu XN,Wang XJ

    更新日期:2020-12-01 00:00:00

  • Hypoxia regulates SOX2 expression to promote prostate cancer cell invasion and sphere formation.

    abstract::SOX2 is an embryonic stem cell marker that in prostate cancer has been associated not only with tumorigenesis but also metastasis. Furthermore hypoxia in primary tumors has been linked to poor prognosis and outcomes in this disease. The goal of the present study was to investigate the impact of hypoxia on SOX2 express...

    journal_title:American journal of cancer research

    pub_type: 杂志文章

    doi:

    authors: Bae KM,Dai Y,Vieweg J,Siemann DW

    更新日期:2016-05-01 00:00:00

  • STAT3β controls inflammatory responses and early tumor onset in skin and colon experimental cancer models.

    abstract::Chronic inflammation is a well-recognized pathogenic factor in tumor initiation and progression. Mice lacking the pro-oncogenic transcription factor STAT3 were shown to be protected from both colitis-associated and epidermal cancers induced by the AOM/DSS and DMBA/TPA protocols, respectively. However, these murine mod...

    journal_title:American journal of cancer research

    pub_type: 杂志文章

    doi:

    authors: Marino F,Orecchia V,Regis G,Musteanu M,Tassone B,Jon C,Forni M,Calautti E,Chiarle R,Eferl R,Poli V

    更新日期:2014-09-06 00:00:00

  • Pleiotropic role of macrophage migration inhibitory factor in cancer.

    abstract::Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine that serves many roles in inflammation and immunity; however, it is also involved in carcinogenesis. This is a review of the clinical and experimental data published on MIF and its role in various types of cancers such as glioblastomas, lung canc...

    journal_title:American journal of cancer research

    pub_type: 杂志文章

    doi:

    authors: Guda MR,Rashid MA,Asuthkar S,Jalasutram A,Caniglia JL,Tsung AJ,Velpula KK

    更新日期:2019-12-01 00:00:00

  • A retrospective study of risk and prognostic factors in relation to lower respiratory tract infection in elderly lung cancer patients.

    abstract::Lung cancer (LCa) is one of the most common and deadly malignancies in elderly patients. During the course of the disease, these patients frequently present with lower respiratory tract infection. Therefore, this study aims to investigate the clinical features of lower respiratory tract infection in elderly LCa patien...

    journal_title:American journal of cancer research

    pub_type: 杂志文章

    doi:

    authors: Qiao D,Wang Z,Lu Y,Wen X,Li H,Zhao H

    更新日期:2014-12-15 00:00:00

  • A sex-dimorphic mouse model of esophageal squamous cell carcinoma.

    abstract::Sexual dimorphism in the incidence of human esophageal cancer, including both esophageal adenocarcinoma and squamous cell carcinoma, shows male dominancy. However, the mechanisms that underlie sexual dimorphism of esophageal cancer have been understudied in vivo due to the lack of sex-dimorphic mouse models. Here, we ...

    journal_title:American journal of cancer research

    pub_type: 杂志文章

    doi:

    authors: Zheng D,Li Z

    更新日期:2019-02-01 00:00:00

  • Elevated RABEX-5 expression predicts poor prognosis in non-small-cell lung cancer.

    abstract::RABEX-5 has been studied in various solid tumors, but its role in non-small-cell lung cancer (NSCLC) remains unknown. This study is aimed to investigate the expression, the potential relevance to clinicopathological characters and prognostic significance of RABEX-5 in patients with NSCLC. A total of 120 NSCLC patients...

    journal_title:American journal of cancer research

    pub_type: 杂志文章

    doi:

    authors: Zhang F,Jia Y,Kong F,Hu G,Cai Q,Xu T

    更新日期:2015-08-15 00:00:00

  • Depletion of gamma-glutamylcyclotransferase in cancer cells induces autophagy followed by cellular senescence.

    abstract::Gamma-glutamylcyclotransferase (GGCT) was originally identified as a protein highly expressed in bladder cancer tissues by proteomic analysis, and its higher expression in a variety of cancers compared to normal tissues have been shown. Depletion of GGCT in various cancer cells results in antiproliferative effects bot...

    journal_title:American journal of cancer research

    pub_type: 杂志文章

    doi:

    authors: Taniguchi K,Matsumura K,Ii H,Kageyama S,Ashihara E,Chano T,Kawauchi A,Yoshiki T,Nakata S

    更新日期:2018-04-01 00:00:00

  • Epigenetic modulation of insulin-like growth factor-II overexpression by hepatitis B virus X protein in hepatocellular carcinoma.

    abstract::Hepatitis B virus X protein (HBx) is involved in the pathogenesis of hepatocellular carcinoma (HCC). Overexpression of the transcripts from the P3 and P4 promoters of the insulin-like growth factor-II (IGF-II) gene is observed in HCC. The present study investigated the involvement of HBx in IGF-II overexpression and i...

    journal_title:American journal of cancer research

    pub_type: 杂志文章

    doi:

    authors: Liu XY,Tang SH,Wu SL,Luo YH,Cao MR,Zhou HK,Jiang XW,Shu JC,Bie CQ,Huang SM,Zheng ZH,Gao F

    更新日期:2015-02-15 00:00:00

  • Cisplatin loaded albumin mesospheres for lung cancer treatment.

    abstract::The low solubility of cisplatin in aqueous solution limits the treatment effectiveness and the application of cisplatin in various kinds of drug-eluting devices. Although cisplatin has a high solubility in Dimethyl sulfoxide (DMSO), the toxicity of cisplatin can be greatly reduced while dissolved in DMSO. In this stud...

    journal_title:American journal of cancer research

    pub_type: 杂志文章

    doi:

    authors: Lee HY,Mohammed KA,Goldberg EP,Kaye F,Nasreen N

    更新日期:2015-01-15 00:00:00

  • Combined efficacy and mechanism of trifluridine and SN-38 in a 5-FU-resistant human colorectal cancer cell lines.

    abstract::Trifluridine/tipiracil (FTD/TPI or TFTD, also known as TAS-102) with a molar ratio of 1:0.5, is a novel combination of FTD, an antineoplastic thymidine analog, and TPI, an inhibitor of thymidine phosphorylase. It has been approved as a treatment for unresectable advanced or recurrent colorectal cancer. Irinotecan (CPT...

    journal_title:American journal of cancer research

    pub_type: 杂志文章

    doi:

    authors: Matsuoka K,Takechi T

    更新日期:2017-12-01 00:00:00

  • Erratum: MicroRNA-338-3p suppresses metastasis of lung cancer cells by targeting the EMT regulator Sox4.

    abstract::[This corrects the article on p. 127 in vol. 6, PMID: 27186391.]. ...

    journal_title:American journal of cancer research

    pub_type: 已发布勘误

    doi:

    authors: Li Y,Chen P,Zu L,Liu B,Wang M,Zhou Q

    更新日期:2016-07-01 00:00:00

  • Downregulation of ACSM3 promotes metastasis and predicts poor prognosis in hepatocellular carcinoma.

    abstract::Understanding mechanisms of cancer metastasis is crucial for reduction of cancer mortality. Acyl-CoA medium-chain synthetase 3 (ACSM3) is an acyl-CoA synthetase which takes part in the first step of fatty acid metabolism. However, the expression, clinical significance and biological function of ACSM3 remain unknown in...

    journal_title:American journal of cancer research

    pub_type: 杂志文章

    doi:

    authors: Ruan HY,Yang C,Tao XM,He J,Wang T,Wang H,Wang C,Jin GZ,Jin HJ,Qin WX

    更新日期:2017-03-01 00:00:00

  • Changes of TCR repertoire diversity in colorectal cancer after Erbitux (cetuximab) in combination with chemotherapy.

    abstract::We have previous found a positive correlation between post-therapy TCR repertoire normalization and remission of colorectal cancer (CRC) patients following fluorouracil, leucovorin, and irinotecan (FOLFIRI) plus bevacizumab or Rh-endostatin therapy. To further define the TCR repertoire diversity changes following trea...

    journal_title:American journal of cancer research

    pub_type: 杂志文章

    doi:

    authors: Luo W,He WT,Wen Q,Chen S,Wu J,Chen XP,Ma L

    更新日期:2014-11-19 00:00:00

  • Prognostic significance of minichromosome maintenance proteins in breast cancer.

    abstract::A role for the minichromosome maintenance (MCM) proteins in cancer initiation and progression is slowly emerging. Functioning as a complex to ensure a single chromosomal replication per cell cycle, the six family members have been implicated in several neoplastic disease states, including breast cancer. Our study aim ...

    journal_title:American journal of cancer research

    pub_type: 杂志文章

    doi:

    authors: Kwok HF,Zhang SD,McCrudden CM,Yuen HF,Ting KP,Wen Q,Khoo US,Chan KY

    更新日期:2014-12-15 00:00:00

  • Muc1 promotes migration and lung metastasis of melanoma cells.

    abstract::Early stages of melanoma can be successfully treated by surgical resection of the tumor, but there is still no effective treatment once it is progressed to metastatic phases. Although growing family of both melanoma metastasis promoting and metastasis suppressor genes have been reported be related to metastasis, the m...

    journal_title:American journal of cancer research

    pub_type: 杂志文章

    doi:

    authors: Wang X,Lan H,Li J,Su Y,Xu L

    更新日期:2015-08-15 00:00:00

  • Long noncoding RNA CASC11 promotes osteosarcoma metastasis by suppressing degradation of snail mRNA.

    abstract::Osteosarcoma (OS) is the most common primary bone tumor in adolescents. Dysregulation of long noncoding RNAs (lncRNAs) is associated with the cancer progression, of which cancer susceptibility candidate 11 (CASC11) has been indicated as an oncogene in several human cancers. However, the underlying mechanisms by which ...

    journal_title:American journal of cancer research

    pub_type: 杂志文章,收录出版

    doi:

    authors: Song K,Yuan X,Li G,Ma M,Sun J

    更新日期:2019-02-01 00:00:00