Inhibition of cytohesin-1 by siRNA leads to reduced IGFR signaling in prostate cancer

Zhang, Weizhong; Gao, Shengxiang; Qin, Hanjiao; Man, Yuhong; Yang, Xiaohua; Cao, Jian; Li, Lisen

doi:10.1590/s0100-879x2011007500072

Cited by 6 publications

(5 citation statements)

References 11 publications

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“…In this assay, we found that inhibiting cytohesins by SecinH3 decreased the invasion and migration of colorectal cancer cells. Researchers have recently reported similar reductions in lung and prostate cancer [6]; [19]; [24]. This reduction can contribute to the down regulation of EGF and IGF-I pathway signal amplification and transduction.…”

Section: Discussionmentioning

confidence: 85%

Cytohesins/ARNO: The Function in Colorectal Cancer Cells

Sun

et al. 2014

PLoS ONE

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Epidermal growth factor (EGF) and insulin-like growth factor-I (IGF-I) are critical regulators of cell differentiation, survival, proliferation, and migration in cancers. This study found that ARNO (cytohesin-2), an activator of the EGF and IGF-I pathways, was more highly expressed in colorectal cancer tissue than in benign adjacent colorectal tissue. When ARNO-siRNA or the chemical inhibitor SecinH3 blocked ARNO, the downstream of the EGF and IGF-I pathways decreased in colorectal cell lines HT29 and HCT116. This blocking also weakened cell proliferation, invasion, and migration in vitro. Furthermore, EGF receptor (EGFR)-dependent colorectal tumor xenografts in nude mouse exerted anti-proliferative and growth suppression effects by injecting secineH3. These data suggested that inhibiting cytohesins or ARNO as cytoplasmic activators of EGFR and IGF-I in colorectal cancer resulted in anti-proliferation, reduced invasion, decreased migration, and suppressed growth in vivo and in vitro. Therefore, cytohesins or ARNO may be a potential therapy target for some colorectal cancer.

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Section: Discussionmentioning

confidence: 85%

Cytohesins/ARNO: The Function in Colorectal Cancer Cells

Sun

et al. 2014

PLoS ONE

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“…Previous investigations of cytohesins in the prostate were limited to two studies without regarding BPH or smooth muscle contraction (64,66). Recently, cytohesin expression was detected in the human myometrium; however, no contraction experiments were performed in that study (34).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of smooth muscle contraction and ARF6 activity by the inhibitor for cytohesin GEFs, secinH3, in the human prostate

Herlemann

Keller

Schott

et al. 2018

American Journal of Physiology-Renal Physiology

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Prostate smooth muscle contraction is critical for etiology and treatment of male lower urinary tract symptoms (LUTS) and is promoted by small monomeric GTPases (RhoA and Rac). GTPases may be activated by guanosine nucleotide exchange factors (GEFs). GEFs of the cytohesin family may indirectly activate Rac, or ADP ribosylation factor (ARF) GTPases directly. Here we investigated the expression of cytohesin family GEFs and effects of the cytohesin inhibitor Sec7 inhibitor H3 (secinH3) on smooth muscle contraction and GTPase activities in human prostate tissues. Of all four cytohesin isoforms, cytohesin-1 and -2 showed the highest expression in real-time PCR. Western blot and fluorescence staining suggested that cytohesin-2 may be the predominant isoform in prostate smooth muscle cells. Contractions induced by norepinephrine, the α-adrenoceptor agonist phenylephrine, the thromboxane A analog U-46619 , and endothelin-1 and -3, as well as neurogenic contractions induced by electric field stimulation (EFS), were reduced by secinH3 (30 µM). Inhibition of EFS-induced contractions appeared to have efficacy similar to that of inhibition by the α-adrenoceptor antagonist tamsulosin (300 nM). Combined application of secinH3 plus tamsulosin caused larger inhibition of EFS-induced contractions than tamsulosin alone. Pull-down assays demonstrated inhibition of the small monomeric GTPase ARF6 by secinH3, but no inhibition of RhoA or Rac1. In conclusion, we suggest that a cytohesin-ARF6 pathway takes part in smooth muscle contraction. This may open attractive new possibilities in medical treatment of male LUTS.

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“…Prior to the treatment with ursolic acid, Akt1 phosphorylation at threonine 308 was overexpressed in the control cells (26). The hyperactivated pAkt1 exhibited a serine-threonine protein kinase activity and triggered the cascade enzymes, resulting in an increased phosphorylation of IκBα at serines 32 and 36. pIκBα was disassociated from NF-κB, resulting in increased NF-κBp65 at the mRNA and protein levels.…”

Section: Discussionmentioning

confidence: 99%

“…The reaction conditions were as follows: 40 cycles of 95˚C for 30 sec, 58˚C for 60 sec and 72˚C for 60 sec. The primers were designed based on the GenBank sequence using Beacon Designer 7 (Premier Biosoft, Palo Alto, CA, USA) and the primer sequences were verified using Blast (26). Primer synthesis and DNA sequencing were performed by Shanghai Sangon Biotechnology (Shanghai, China).…”

Section: Methodsmentioning

confidence: 99%

Ursolic acid induces apoptosis via Akt/NF-κB signaling suppression in T24 human bladder cancer cells

Gai¹,

Cai²,

Wang³

et al. 2013

Molecular Medicine Reports

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The Akt/NF-κB pathway is involved in numerous anti‑apoptotic and drug resistance events which occur in various types of bladder cancer. The present study investigated the role of ursolic acid in the regulation of anti-apoptotic Akt and NF-κBp65 signaling. T24 human bladder cancer cells were treated with ursolic acid at final concentrations of 12.5, 25 or 50 µmol/l for 48 h. Quantitative PCR (qPCR) and western blotting were performed to detect mRNA and protein expression, respectively. The results showed that anti-apoptotic phospho-Akt1 (pAkt1), phospho-IκBα (pIκBα), NF-κBp65 and Bcl-2 were inhibited and pro-apoptotic caspase-3 was upregulated in a dose‑dependent manner. A 50 µmol/l dose of ursonic acid decreased the mRNA expression levels of anti-apoptotic NF-κBp65 and Bcl-2 0.17 (8.9/52.6)-fold and 0.22 (9.5/42.3)‑fold, respectively. The pro-apoptotic caspase-3 mRNA expression levels were upregulated 4.78 (38.7/8.1)-fold. The anti-apoptotic pAkt1, pIκBα, NF-κBp65 and Bcl-2 protein levels were downregulated to 5.1 (blot grayscales vs. control at 32.3), 3.2 (vs. 24.2), 8.5 (vs. 45.1) and 9.2 (vs. 40.3). The protein levels of pro-apoptotic caspase-3 were upregulated to 20.7 (vs. 4.7). The proliferative activity of T24 cells treated with 12.5, 25.0 and 50.0 µmol/l ursolic acid was significantly reduced compared with that of control cells (83.8, 56.2 and 31.5 vs. 97.6%, respectively, P<0.05 for each). In conclusion, ursolic acid is important in inducing apoptosis via the suppression of Akt/NF-κB signaling in T24 human bladder cancer cells and this occurs in a dose-dependent manner. Ursolic acid may therefore serve as a naturally occurring candidate drug for the prevention and treatment of bladder cancer.

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Inhibition of cytohesin-1 by siRNA leads to reduced IGFR signaling in prostate cancer

Cited by 6 publications

References 11 publications

Cytohesins/ARNO: The Function in Colorectal Cancer Cells

Cytohesins/ARNO: The Function in Colorectal Cancer Cells

Inhibition of smooth muscle contraction and ARF6 activity by the inhibitor for cytohesin GEFs, secinH3, in the human prostate

Ursolic acid induces apoptosis via Akt/NF-κB signaling suppression in T24 human bladder cancer cells

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