Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Oncology Letters
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-1074 Online ISSN: 1792-1082
Journal Cover
March-2019 Volume 17 Issue 3

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
March-2019 Volume 17 Issue 3

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

UNBS5162 inhibits SKOV3 ovarian cancer cell proliferation by regulating the PI3K/AKT signalling pathway

  • Authors:
    • Qiang Wang
    • Wei Shi
  • View Affiliations / Copyright

    Affiliations: Department of Gynecology and Obstetrics, The Second Hospital of Jilin University, Changchun, Jilin 130000, P.R. China, Department of Gynecology and Obstetrics, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250013, P.R. China
  • Pages: 2976-2982
    |
    Published online on: January 4, 2019
       https://doi.org/10.3892/ol.2019.9890
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Ovarian cancer is the gynaecological malignancy with the highest mortality rate worldwide, and effective and safe therapeutic methods are limited. UNBS5162, a derivative of naphthalimide, has a clear inhibitory effect on the proliferation of various tumour cells in vitro and in vivo as a pan‑antagonist of CXC chemokine ligand expression, but whether it serves a function in ovarian cancer remains unclear. The aim of the present study was to determine the effects of UNBS5162 on the proliferation, migration and invasion of ovarian cancer cells. The cell viability was detected using a Cell Counting Kit‑8 (CCK‑8) assay. The invasion and migration of SKOV3 cells were determined using Transwell assays. Cell apoptosis was determined using flow cytometry. The apoptosis‑associated proteins and associated factors, such as phosphoinositide 3‑kinase (PI3K)/protein kinase B (AKT) signalling pathway members, were detected using western blot analysis. The CCK‑8 assay revealed that SKOV3 cell viability was affected by UNBS5162 in a dose‑ and time‑dependent manner. In Transwell assays, UNBS5162 inhibited cell invasion and migration. Furthermore, it was identified that UNBS5162 markedly increased the apoptosis rate of SKOV3 cells. Simultaneously, the expression of the anti‑apoptotic protein B‑cell lymphoma 2 (Bcl‑2) was decreased and the expression of the pro‑apoptotic proteins active caspase‑3 and Bcl‑2‑associated X protein were increased in SKOV3 cells treated with UNBS5162. In addition, the expression levels of phospho (p‑)AKT/total AKT, p‑mammalian target of rapamycin (mTOR)/total mTOR, p‑p70 S6 kinase (p70S6K)/total p70S6K and cyclin D1 were decreased in the UNBS5162‑treated group. The results of the present study indicated that UNBS5162 inhibits proliferation, migration and invasion, and induces apoptosis in ovarian cancer cells, which may be regulated by the PI3K/AKT signalling pathway. These results suggest that UNBS5162 may be a potential novel drug for clinical ovarian cancer treatment.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Worzfeld T, Pogge von Strandmann E, Huber M, Adhikary T, Wagner U, Reinartz S and Müller R: The unique molecular and cellular microenvironment of ovarian cancer. Front Oncol. 7:242017. View Article : Google Scholar : PubMed/NCBI

2 

Yan B, Yin F, Wang QI, Zhang W and Li LI: Integration and bioinformatics analysis of DNA-methylated genes associated with drug resistance in ovarian cancer. Oncol Lett. 12:157–166. 2016. View Article : Google Scholar : PubMed/NCBI

3 

Faber MT, Kjaer SK, Dehlendorff C, Chang-Claude J, Andersen KK, Høgdall E, Webb PM, Jordan SJ; Australian Cancer Study (Ovarian Cancer); Australian Ovarian Cancer Study Group, ; et al: Cigarette smoking and risk of ovarian cancer: A pooled analysis of 21 case-control studies. Cancer Causes Control. 24:989–1004. 2013. View Article : Google Scholar : PubMed/NCBI

4 

Weidle UH, Birzele F, Kollmorgen G and Rueger R: Mechanisms and targets involved in dissemination of ovarian cancer. Cancer Genomics Proteomics. 13:407–423. 2016. View Article : Google Scholar : PubMed/NCBI

5 

Correa RJ, Valdes YR, Peart TM, Fazio EN, Bertrand M, McGee J, Préfontaine M, Sugimoto A, DiMattia GE and Shepherd TG: Combination of AKT inhibition with autophagy blockade effectively reduces ascites-derived ovarian cancer cell viability. Carcinogenesis. 35:1951–1961. 2014. View Article : Google Scholar : PubMed/NCBI

6 

Li S, Xu S, Tang Y, Ding S, Zhang J, Wang S, Zhou G, Zhou C and Li X: Synthesis, anticancer activity and DNA-binding properties of novel 4-pyrazolyl-1,8-naphthalimide derivatives. Bioorg Med Chem Lett. 24:586–590. 2014. View Article : Google Scholar : PubMed/NCBI

7 

Zhao L, Li J, Li Y, Liu J, Wirth T and Li Z: Selenium-containing naphthalimides as anticancer agents: Design, synthesis and bioactivity. Bioorg Med Chem. 20:2558–2563. 2012. View Article : Google Scholar : PubMed/NCBI

8 

Ingrassia L, Lefranc F, Kiss R and Mijatovic T: Naphthalimides and azonafides as promising anti-cancer agents. Curr Med Chem. 16:1192–1213. 2009. View Article : Google Scholar : PubMed/NCBI

9 

Dumont P, Ribaucour F, Quaquebeke EV, Darro F and Kiss R: UNBS3157, a new amonafide derivative with improved in vivo efficacy and decreased toxicity. Cancer Res. 66 Supp:11052006.PubMed/NCBI

10 

Van Quaquebeke E, Mahieu T, Dumont P, Dewelle J, Ribaucour F, Simon G, Sauvage S, Gaussin JF, Tuti J, El Yazidi M, et al: 2,2,2-Trichloro-N-({2-[2-(dimethylamino)ethyl]-1,3-dioxo-2,3- dihydro-1H-benzo[de]isoquinolin-5-yl}carbamoyl)acetamide (UNBS3157), a novel nonhematotoxic naphthalimide derivative with potent antitumor activity. J Med Chem. 50:4122–4134. 2007. View Article : Google Scholar : PubMed/NCBI

11 

Liu C, Xing J and Gao Y: UNBS5162 inhibits the proliferation of human A549 non-small-cell lung cancer cells by promoting apoptosis. Thorac Cancer. 9:105–111. 2018. View Article : Google Scholar : PubMed/NCBI

12 

He D and Zhang S: UNBS5162 inhibits the proliferation of esophageal cancer squamous cells via the PI3K/AKT signalling pathway. Mol Med Rep. 17:549–555. 2018.PubMed/NCBI

13 

Wang B, Shen J and Wang J: UNBS5162 inhibits proliferation of human retinoblastoma cells by promoting cell apoptosis. Onco Targets Ther. 10:5303–5309. 2017. View Article : Google Scholar : PubMed/NCBI

14 

Mijatovic T, Mahieu T, Bruyere C, De Nève N, Dewelle J, Simon G, Dehoux MJ, van der Aar E, Haibe-Kains B, Bontempi G, et al: UNBS5162, a novel naphthalimide that decreases CXCL chemokine expression in experimental prostate cancers. Neoplasia. 10:573–586. 2008. View Article : Google Scholar : PubMed/NCBI

15 

Agudelo D, Bourassa P, Bérubé G and Tajmir-Riahi HA: Intercalation of antitumor drug doxorubicin and its analogue by DNA duplex: Structural features and biological implications. Int J Biol Macromol. 66:144–150. 2014. View Article : Google Scholar : PubMed/NCBI

16 

Gellerman G: Recent developments in the synthesis and applications of anticancer amonafide derivatives. A mini review. Letters Drug Design Discov. 13:47–63. 2016. View Article : Google Scholar

17 

Zhao J, Lu M, Lai H, Lu H, Lalevée J, Barner-Kowollik C, Stenzel MH and Xiao P: Delivery of amonafide from fructose-coated nanodiamonds by oxime ligation for treatment of human breast cancer. Biomacromolecules. 19:481–489. 2018. View Article : Google Scholar : PubMed/NCBI

18 

Ge C, Chang L, Zhao Y, Chang C, Xu X, He H, Wang Y, Dai F, Xie S and Wang C: Design, synthesis and evaluation of naphthalimide derivatives as potential anticancer agents for hepatocellular carcinoma. Molecules. 22:E3422017. View Article : Google Scholar : PubMed/NCBI

19 

Mahieu T, Mijatovic T, Quaquebeke EV, Lefranc F, Vynckt FV, Darro F and Kiss R: UNBS5162 is a novel naphthalimide derivative that induces autophagy and senescence in human prostate cancer cells. Mol Cancer Ther. 6:3373S2007.

20 

Antonini I, Volpini R, Dal Ben D, Lambertucci C and Cristalli G: Design, synthesis, and biological evaluation of new mitonafide derivatives as potential antitumor drugs. Bioorg Med Chem. 16:8440–8446. 2008. View Article : Google Scholar : PubMed/NCBI

21 

Mahadevan D, Northfelt DW, Chalasani P, Rensvold D, Kurtin S, Von Hoff DD, Borad MJ and Tibes R: Phase I trial of UNBS5162, a novel naphthalimide in patients with advanced solid tumors or lymphoma. Int J Clin Oncol. 18:934–941. 2013. View Article : Google Scholar : PubMed/NCBI

22 

Mei JM and Niu CS: Effects of CDNF on 6-OHDA-induced apoptosis in PC12 cells via modulation of Bcl-2/Bax and caspase-3 activation. Neurol Sci. 35:1275–1280. 2014. View Article : Google Scholar : PubMed/NCBI

23 

Zhuang RJ, Ma J, Shi X, Ju F, Ma SP, Wang L, Cheng BF, Ma YW, Wang M, Li T, et al: Cold-inducible protein RBM3 protects UV irradiation-induced apoptosis in neuroblastoma cells by affecting p38 and JNK pathways and Bcl2 family proteins. J Mol Neurosci. 63:142–151. 2017. View Article : Google Scholar : PubMed/NCBI

24 

Nakamura Y, Ise K, Yamazaki Y, Fujishima F, McNamara KM and Sasano H: Serotonin receptor 4 (5-hydroxytryptamine receptor Type 4) regulates expression of estrogen receptor beta and cell migration in hormone-naive prostate cancer. Indian J Pathol Microbiol. 60:33–37. 2017.PubMed/NCBI

25 

Jordan VC: The new biology of estrogen-induced apoptosis applied to treat and prevent breast cancer. Endocr Relat Cancer. 22:R1–R31. 2015. View Article : Google Scholar : PubMed/NCBI

26 

Shukla S, Fu P and Gupta S: Apigenin induces apoptosis by targeting inhibitor of apoptosis proteins and Ku70-Bax interaction in prostate cancer. Apoptosis. 19:883–894. 2014. View Article : Google Scholar : PubMed/NCBI

27 

Zhou ZW, Li XX, He ZX, Pan ST, Yang Y, Zhang X, Chow K, Yang T, Qiu JX, Zhou Q, et al: Induction of apoptosis and autophagy via sirtuin1- and PI3K/Akt/mTOR-mediated pathways by plumbagin in human prostate cancer cells. Drug Des Devel Ther. 9:1511–1554. 2015. View Article : Google Scholar : PubMed/NCBI

28 

Akinleye A, Avvaru P, Furqan M, Song Y and Liu D: Phosphatidylinositol 3-kinase (PI3K) inhibitors as cancer therapeutics. J Hematol Oncol. 6:882013. View Article : Google Scholar : PubMed/NCBI

29 

Fang WL, Huang KH, Lan YT, Lin CH, Chang SC, Chen MH, Chao Y, Lin WC, Lo SS, Li AF, et al: Mutations in PI3K/AKT pathway genes and amplifications of PIK3CA are associated with patterns of recurrence in gastric cancers. Oncotarget. 7:6201–6220. 2016. View Article : Google Scholar : PubMed/NCBI

30 

Huang J, Zhang L, Greshock J, Colligon TA, Wang Y, Ward R, Katsaros D, Lassus H, Butzow R, Godwin AK, et al: Frequent genetic abnormalities of the PI3K/AKT pathway in primary ovarian cancer predict patient outcome. Genes Chromosomes Cancer. 50:606–618. 2011. View Article : Google Scholar : PubMed/NCBI

31 

Zhang L, Huo X, Liao Y, Yang F, Gao L and Cao L: Zeylenone, a naturally occurring cyclohexene oxide, inhibits proliferation and induces apoptosis in cervical carcinoma cells via PI3K/AKT/mTOR and MAPK/ERK pathways. Sci Rep. 7:16692017. View Article : Google Scholar : PubMed/NCBI

32 

Halacli SO and Dogan AL: FOXP1 regulation via the PI3K/Akt/p70S6K signalling pathway in breast cancer cells. Oncol Lett. 9:1482–1488. 2015. View Article : Google Scholar : PubMed/NCBI

33 

Wang HY, Yang SL, Liang HF and Li CH: HBx protein promotes oval cell proliferation by up-regulation of cyclin D1 via activation of the MEK/ERK and PI3K/Akt pathways. Int J Mol Sci. 15:3507–3518. 2014. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Wang Q and Shi W: UNBS5162 inhibits SKOV3 ovarian cancer cell proliferation by regulating the PI3K/AKT signalling pathway. Oncol Lett 17: 2976-2982, 2019.
APA
Wang, Q., & Shi, W. (2019). UNBS5162 inhibits SKOV3 ovarian cancer cell proliferation by regulating the PI3K/AKT signalling pathway. Oncology Letters, 17, 2976-2982. https://doi.org/10.3892/ol.2019.9890
MLA
Wang, Q., Shi, W."UNBS5162 inhibits SKOV3 ovarian cancer cell proliferation by regulating the PI3K/AKT signalling pathway". Oncology Letters 17.3 (2019): 2976-2982.
Chicago
Wang, Q., Shi, W."UNBS5162 inhibits SKOV3 ovarian cancer cell proliferation by regulating the PI3K/AKT signalling pathway". Oncology Letters 17, no. 3 (2019): 2976-2982. https://doi.org/10.3892/ol.2019.9890
Copy and paste a formatted citation
x
Spandidos Publications style
Wang Q and Shi W: UNBS5162 inhibits SKOV3 ovarian cancer cell proliferation by regulating the PI3K/AKT signalling pathway. Oncol Lett 17: 2976-2982, 2019.
APA
Wang, Q., & Shi, W. (2019). UNBS5162 inhibits SKOV3 ovarian cancer cell proliferation by regulating the PI3K/AKT signalling pathway. Oncology Letters, 17, 2976-2982. https://doi.org/10.3892/ol.2019.9890
MLA
Wang, Q., Shi, W."UNBS5162 inhibits SKOV3 ovarian cancer cell proliferation by regulating the PI3K/AKT signalling pathway". Oncology Letters 17.3 (2019): 2976-2982.
Chicago
Wang, Q., Shi, W."UNBS5162 inhibits SKOV3 ovarian cancer cell proliferation by regulating the PI3K/AKT signalling pathway". Oncology Letters 17, no. 3 (2019): 2976-2982. https://doi.org/10.3892/ol.2019.9890
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team