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
January-2019 Volume 17 Issue 1

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
January-2019 Volume 17 Issue 1

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 Open Access

Occurrence of senescence-escaping cells in doxorubicin-induced senescence is enhanced by PD0332991, a cyclin-dependent kinase 4/6 inhibitor, in colon cancer HCT116 cells

  • Authors:
    • Kunio Kitada
    • Fengling Pu
    • Masakazu Toi
  • View Affiliations / Copyright

    Affiliations: Department of Breast Surgery, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan
    Copyright: © Kitada et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1153-1159
    |
    Published online on: November 1, 2018
       https://doi.org/10.3892/ol.2018.9657
  • 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

Cancer treatment induces cellular senescence, and it is considered to be one of the factors that determines treatment outcome. Senescence can be efficiently induced in cultured cells by DNA-damaging drugs, including doxorubicin (DOX), cisplatin and etoposide. Cells in senescence cease proliferation; however, it has been demonstrated that colonies that are formed from cells escaping senescence appear in drug-induced senescence; however, the conditions influencing the emergence of such senescence-escaping cells (SECs) remain unclear. The present study aimed to investigate the relevance of the cell cycle phase and colony formation in the DOX-induced senescence of human colon cancer HCT116 cells. After release from serum starvation in the presence of DOX, cells synchronously progressed through the cell cycle and were arrested in the G1 and G2/M phases. The ratio of G1 cells arrested immediately by the treatment of G1 phase cells was positively associated with the number of colony-forming cells. A procedure increasing G1-treated G1-arrested cells enhanced colony formation. Co-treatment of PD0332991 with DOX slowed progression of cells in the G1 phase resulting in enhanced colony formation from the increased G1-treated G1-arrested cells. These results may provide useful insights into understanding the emergence of SECs in drug-induced senescence.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Campisi J: Senescent cells, tumor suppression, and organismal aging: Good citizens, bad neighbors. Cell. 120:513–522. 2005. View Article : Google Scholar : PubMed/NCBI

2 

Collado M and Serrano M: The power and the promise of oncogene-induced senescence markers. Nat Rev Cancer. 6:472–476. 2006. View Article : Google Scholar : PubMed/NCBI

3 

Di Mitri D and Alimonti A: Non-cell-autonomous regulation of cellular senescence in cancer. Trends Cell Biol. 26:215–226. 2016. View Article : Google Scholar : PubMed/NCBI

4 

Wang X, Tsao SW, Wong YC and Cheung AL: Induction of senescent-like growth arrest as a new target in anticancer treatment. Curr Cancer Drug Targets. 3:153–159. 2003. View Article : Google Scholar : PubMed/NCBI

5 

Tchkonia T, Zhu Y, van Deursen J, Campisi J and Kirkland JL: Cellular senescence and the senescent secretory phenotype: Therapeutic opportunities. J Clin Invest. 123:966–972. 2013. View Article : Google Scholar : PubMed/NCBI

6 

Ewald JA, Desotelle JA, Wilding G and Jarrard DF: Therapy-induced senescence in cancer. J Natl Cancer Inst. 102:1536–1546. 2010. View Article : Google Scholar : PubMed/NCBI

7 

Petrova NV, Velichko AK, Razin SV and Kantidze OL: Small molecule compounds that induce cellular senescence. Aging Cell. 15:999–1017. 2016. View Article : Google Scholar : PubMed/NCBI

8 

Elmore LW, Rehder CW, Di X, McChesney PA, Jackson-Cook CK, Gewirtz DA and Holt SE: Adriamycin-induced senescence in breast tumor cells involves functional p53 and telomere dysfunction. J Biol Chem. 277:35509–35515. 2002. View Article : Google Scholar : PubMed/NCBI

9 

Sliwinska MA, Mosieniak G, Wolanin K, Babik A, Piwocka K, Magalska A, Szczepanowska J, Fronk J and Sikora E: Induction of senescence with doxorubicin leads to increased genomic instability of HCT116 cells. Mech Ageing Dev. 130:24–32. 2009. View Article : Google Scholar : PubMed/NCBI

10 

Su D, Zhu S, Han X, Feng Y, Huang H, Ren G, Pan L, Zhang Y, Lu J and Huang B: BMP4-Smad signaling pathway mediates adriamycin-induced premature senescence in lung cancer cells. J Biol Chem. 284:12153–12164. 2009. View Article : Google Scholar : PubMed/NCBI

11 

Hamilton E and Infante JR: Targeting CDK4/6 in patients with cancer. Cancer Treat Rev. 45:129–138. 2016. View Article : Google Scholar : PubMed/NCBI

12 

Xu H, Yu S, Liu Q, Yuan X, Mani S, Pestell RG and Wu K: Recent advances of highly selective CDK4/6 inhibitors in breast cancer. J Hematol Oncol. 10:972017. View Article : Google Scholar : PubMed/NCBI

13 

Sherr CJ and Roberts JM: CDK inhibitors: Positive and negative regulators of G1-phase progression. Genes Dev. 13:1501–1512. 1999. View Article : Google Scholar : PubMed/NCBI

14 

Malumbres M, Ortega S and Barbacid M: Genetic analysis of mammalian cyclin-dependent kinases and their inhibitors. Biol Chem. 381:827–838. 2000. View Article : Google Scholar : PubMed/NCBI

15 

Fry DW, Harvey PJ, Keller PR, Elliott WL, Meade M, Trachet E, Albassam M, Zheng X, Leopold WR, Pryer NK, et al: Specific inhibition of cyclin-dependent kinase 4/6 by PD 0332991 and associated antitumor activity in human tumor xenografts. Mol Cancer Ther. 3:1427–1438. 2004.PubMed/NCBI

16 

Toogood PL, Harvey PJ, Repine JT, Sheehan DJ, VanderWel SN, Zhou H, Keller PR, McNamara DJ, Sherry D, Zhu T, et al: Discovery of a potent and selective inhibitor of cyclin-dependent kinase 4/6. J Med Chem. 48:2388–2406. 2005. View Article : Google Scholar : PubMed/NCBI

17 

Guha M: Cyclin-dependent kinase inhibitors move into Phase III. Nat Rev Drug Discov. 11:892–894. 2012. View Article : Google Scholar : PubMed/NCBI

18 

Kovatcheva M, Liu DD, Dickson MA, Klein ME, O'Connor R, Wilder FO, Socci ND, Tap WD, Schwartz GK, Singer S, et al: MDM2 turnover and expression of ATRX determine the choice between quiescence and senescence in response to CDK4 inhibition. Oncotarget. 6:8226–8243. 2015. View Article : Google Scholar : PubMed/NCBI

19 

Ziemke EK, Dosch JS, Maust JD, Shettigar A, Sen A, Welling TH, Hardiman KM and Sebolt-Leopold JS: Sensitivity of KRAS-mutant colorectal cancers to combination therapy that cotargets MEK and CDK4/6. Clin Cancer Res. 22:405–414. 2016. View Article : Google Scholar : PubMed/NCBI

20 

Chang BD, Xuan Y, Broude EV, Zhu H, Schott B, Fang J and Roninson IB: Role of p53 and p21waf1/cip1 in senescence-like terminal proliferation arrest induced in human tumor cells by chemotherapeutic drugs. Oncogene. 18:4808–4818. 1999. View Article : Google Scholar : PubMed/NCBI

21 

Ben-Porath I and Weinberg RA: The signals and pathways activating cellular senescence. Int J Biochem Cell Biol. 37:961–976. 2005. View Article : Google Scholar : PubMed/NCBI

22 

Dimri GP, Lee X, Basile G, Acosta M, Scott G, Roskelley C, Medrano EE, Linskens M, Rubelj I and Pereira-Smith O: A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc Natl Acad Sci USA. 92:9363–9367. 1995. View Article : Google Scholar : PubMed/NCBI

23 

Trzepacz C, Lowy AM, Kordich JJ and Groden J: Phosphorylation of the tumor suppressor adenomatous polyposis coli (APC) by the cyclin-dependent kinase p34. J Biol Chem. 272:21681–21684. 1997. View Article : Google Scholar : PubMed/NCBI

24 

Mizuno H, Nakanishi Y, Ishii N, Sarai A and Kitada K: A signature-based method for indexing cell cycle phase distribution from microarray profiles. BMC Genomics. 10:1372009. View Article : Google Scholar : PubMed/NCBI

25 

Zieve GW, Turnbull D, Mullins JM and McIntosh JR: Production of large numbers of mitotic mammalian cells by use of the reversible microtubule inhibitor nocodazole. Nocodazole accumulated mitotic cells. Exp Cell Res. 126:397–405. 1980. View Article : Google Scholar : PubMed/NCBI

26 

Long BH and Fairchild CR: Paclitaxel inhibits progression of mitotic cells to G1 phase by interference with spindle formation without affecting other microtubule functions during anaphase and telephase. Cancer Res. 54:4355–4361. 1994.PubMed/NCBI

27 

Erol A: Deciphering the intricate regulatory mechanisms for the cellular choice between cell repair, apoptosis or senescence in response to damaging signals. Cell Signal. 23:1076–1081. 2011. View Article : Google Scholar : PubMed/NCBI

28 

Roos WP, Thomas AD and Kaina B: DNA damage and the balance between survival and death in cancer biology. Nat Rev Cancer. 16:20–33. 2016. View Article : Google Scholar : PubMed/NCBI

29 

Chen X, Lowe M, Herliczek T, Hall MJ, Danes C, Lawrence DA and Keyomarsi K: Protection of normal proliferating cells against chemotherapy by staurosporine-mediated, selective, and reversible G(1) arrest. J Natl Cancer Inst. 92:1999–2008. 2000. View Article : Google Scholar : PubMed/NCBI

30 

Blagosklonny MV and Pardee AB: Exploiting cancer cell cycling for selective protection of normal cells. Cancer Res. 61:4301–4305. 2001.PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Kitada K, Pu F and Toi M: Occurrence of senescence-escaping cells in doxorubicin-induced senescence is enhanced by PD0332991, a cyclin-dependent kinase 4/6 inhibitor, in colon cancer HCT116 cells. Oncol Lett 17: 1153-1159, 2019.
APA
Kitada, K., Pu, F., & Toi, M. (2019). Occurrence of senescence-escaping cells in doxorubicin-induced senescence is enhanced by PD0332991, a cyclin-dependent kinase 4/6 inhibitor, in colon cancer HCT116 cells. Oncology Letters, 17, 1153-1159. https://doi.org/10.3892/ol.2018.9657
MLA
Kitada, K., Pu, F., Toi, M."Occurrence of senescence-escaping cells in doxorubicin-induced senescence is enhanced by PD0332991, a cyclin-dependent kinase 4/6 inhibitor, in colon cancer HCT116 cells". Oncology Letters 17.1 (2019): 1153-1159.
Chicago
Kitada, K., Pu, F., Toi, M."Occurrence of senescence-escaping cells in doxorubicin-induced senescence is enhanced by PD0332991, a cyclin-dependent kinase 4/6 inhibitor, in colon cancer HCT116 cells". Oncology Letters 17, no. 1 (2019): 1153-1159. https://doi.org/10.3892/ol.2018.9657
Copy and paste a formatted citation
x
Spandidos Publications style
Kitada K, Pu F and Toi M: Occurrence of senescence-escaping cells in doxorubicin-induced senescence is enhanced by PD0332991, a cyclin-dependent kinase 4/6 inhibitor, in colon cancer HCT116 cells. Oncol Lett 17: 1153-1159, 2019.
APA
Kitada, K., Pu, F., & Toi, M. (2019). Occurrence of senescence-escaping cells in doxorubicin-induced senescence is enhanced by PD0332991, a cyclin-dependent kinase 4/6 inhibitor, in colon cancer HCT116 cells. Oncology Letters, 17, 1153-1159. https://doi.org/10.3892/ol.2018.9657
MLA
Kitada, K., Pu, F., Toi, M."Occurrence of senescence-escaping cells in doxorubicin-induced senescence is enhanced by PD0332991, a cyclin-dependent kinase 4/6 inhibitor, in colon cancer HCT116 cells". Oncology Letters 17.1 (2019): 1153-1159.
Chicago
Kitada, K., Pu, F., Toi, M."Occurrence of senescence-escaping cells in doxorubicin-induced senescence is enhanced by PD0332991, a cyclin-dependent kinase 4/6 inhibitor, in colon cancer HCT116 cells". Oncology Letters 17, no. 1 (2019): 1153-1159. https://doi.org/10.3892/ol.2018.9657
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