Skip to main content
SpringerLink
Log in

Pine needle hexane extract promote cell cycle arrest and premature senescence via p27KIP1 upregulation gastric cancer cells

  • Published:
Food Science and Biotechnology Aims and scope Submit manuscript

Abstract

Pinus densiflora sieb. et zucc.(pine needle) is a traditional medicine used in several East Asian countries. However, the efficacy of pine needle has rarely been reported. In this study showed that the anti-proliferative effects and the mechanisms of hexane layer of pine needle MeOH extract (PNH) on gastric cancer cells. At first, PNH inhibited the proliferation of gastric cancer cells in a dose-dependent manner. Moreover, PNH treatment induced G1 phase cell cycle arrest through the increased p27KIP1 expression and decreased cyclin dependent kinase (CDKs) activity. Furthermore, PNH treatment induced premature senescence without oncogenic stress, through the expression of p27KIP1 and Skp2. Taken together, these results showed that PNH inhibited gastric cancer cell proliferation through the induction of G1-cell cycle arrest and premature senescence via induced p27KIP1 expression, as controlled by Skp2 reduction. Also, PNH could be a candidate for anti-gastric cancer treatment and may be useful in the development of anti-gastric cancer drugs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Bae KH. The Medicinal Plants of Korea. Kyo-Hak, Seoul (2000)

    Google Scholar 

  • Beausejour CM, Campisi J. Ageing: balancing regeneration and cancer. Nature 443: 404-405 (2006)

    Article  CAS  Google Scholar 

  • Braig M, Lee S, Loddenkemper C, Rudolph C, Peters AH, Schlegelberger B, Stein H, Dorken B, Jenuwein T, Schmitt CA. Oncogene-induced senescence as an initial barrier in lymphoma development. Nature 436: 660-665 (2005)

    Article  CAS  Google Scholar 

  • Braig M, Schmitt CA. Oncogene-induced senescence: putting the brakes on tumor development. Cancer Res. 66: 2881-2884 (2006)

    Article  CAS  Google Scholar 

  • Choi EM. Antinociceptive and antiinflammatory activities of pine (Pinus densiflora) pollen extract. Phytother. Res. 21: 471-475 (2007)

    Article  Google Scholar 

  • Collado M, Blasco MA, Serrano M. Cellular senescence in cancer and aging. Cell 130: 223-233 (2007)

    Article  CAS  Google Scholar 

  • Coqueret O. New roles for p21 and p27 cell-cycle inhibitors: a function for each cell compartment? Trends Cell Biol. 13: 65-70 (2003)

    Article  CAS  Google Scholar 

  • Ewald JA, Desotelle JA, Wilding G, Jarrard DF. Therapy-induced senescence in cancer. J. Natl. Cancer Inst. 102: 1536-1546 (2010)

    Article  CAS  Google Scholar 

  • Feitelson MA, Arzumanyan A, Kulathinal RJ, Blain SW, Holcombe RF, Mahajna J, Marino M, Martinez-Chantar ML, Nawroth R, Sanchez-Garcia I, Sharma D, Saxena NK, Singh N, Vlachostergios PJ, Guo S, Honoki K, Fujii H, Georgakilas AG, Bilsland A, Amedei A, Niccolai E, Amin A, Ashraf SS, Boosani CS, Guha G, Ciriolo MR, Aquilano K, Chen S, Mohammed SI, Azmi AS, Bhakta D, Halicka D, Keith WN, Nowsheen S. Sustained proliferation in cancer: Mechanisms and novel therapeutic targets. Semin. Cancer Biol. 35 Suppl: S25-S54 (2015)

    Article  Google Scholar 

  • Hanahan D, Weinberg RA. The hallmarks of cancer. Cell 100: 57-70 (2000)

    Article  CAS  Google Scholar 

  • Kim HY, Cho Y, Kang H, Yim YS, Kim SJ, Song J, Chun KH. Targeting the WEE1 kinase as a molecular targeted therapy for gastric cancer. Oncotarget 7: 49902-49916 (2016)

    Article  Google Scholar 

  • Kim SJ, Lee HW, Kang HG, La SH, Choi IJ, Ro JY, Bresalier RS, Song J, Chun KH. Ablation of galectin-3 induces p27(KIP1)-dependent premature senescence without oncogenic stress. Cell Death Differ. 21: 1769-1779 (2014)

    Article  CAS  Google Scholar 

  • Kim YS, Shin DW. Volatile components and antibacterial effects of pine needle (Pinus densiflora S. and Z.) extracts. Food Microbiol. 22: 37-45 (2005)

    Article  CAS  Google Scholar 

  • Kwak CS, Moon SC, Lee MS. Antioxidant, antimutagenic, and antitumor effects of pine needles (Pinus densiflora). Nutr. Cancer 56: 162-171 (2006)

    Article  CAS  Google Scholar 

  • Lee HJ, Yang HK, Ahn YO. Gastric cancer in Korea. Gastric Cancer 5: 177-182 (2002)

    Article  Google Scholar 

  • Lee S, Kim WB, Park SH, Kim M, Kim D, Park J, Hwang DY, Lee H. Biological properties of butanol extracts from green pine cone of Pinus densiflora. Food Sci. Biotechnol. 27: 1485-1492 (2018)

    Article  CAS  Google Scholar 

  • Lim L, Michael M, Mann GB, Leong T. Adjuvant therapy in gastric cancer. J. Clin. Oncol. 23: 6220-6232 (2005)

    Article  CAS  Google Scholar 

  • Longley DB, Harkin DP, Johnston PG. 5-fluorouracil: mechanisms of action and clinical strategies. Nat. Rev. Cancer 3: 330-338 (2003)

    Article  CAS  Google Scholar 

  • Nevins JR. The Rb/E2F pathway and cancer. Hum. Mol. Genet. 10: 699-703 (2001)

    Article  CAS  Google Scholar 

  • Osman I, Drobnjak M, Fazzari M, Ferrara J, Scher HI, Cordon-Cardo C. Inactivation of the p53 pathway in prostate cancer: impact on tumor progression. Clin. Cancer Res. 5: 2082-2088 (1999)

    CAS  PubMed  Google Scholar 

  • Schmitt CA. Cellular senescence and cancer treatment. Biochim. Biophys. Acta 1775: 5-20 (2007)

    CAS  PubMed  Google Scholar 

  • Schwartz GK, Shah MA. Targeting the cell cycle: a new approach to cancer therapy. J. Clin. Oncol. 23: 9408-9421 (2005)

    Article  CAS  Google Scholar 

  • Shay JW, Wright WE. Hallmarks of telomeres in ageing research. J. Pathol. 211: 114-123 (2007)

    Article  CAS  Google Scholar 

  • Sherr CJ. Cancer cell cycles. Science 274: 1672-1677 (1996)

    Article  CAS  Google Scholar 

  • Steller H. Mechanisms and genes of cellular suicide. Science 267: 1445-1449 (1995)

    Article  CAS  Google Scholar 

  • Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J. Clin. 65: 87-108 (2015)

    Article  Google Scholar 

  • Toyoshima H, Hunter T. p27, a novel inhibitor of G1 cyclin-Cdk protein kinase activity, is related to p21. Cell 78: 67-74 (1994)

    Article  CAS  Google Scholar 

  • Viglietto G, Motti ML, Fusco A. Understanding p27(kip1) deregulation in cancer: down-regulation or mislocalization. Cell Cycle 1: 394-400 (2002)

    Article  CAS  Google Scholar 

  • Waldman T, Zhang Y, Dillehay L, Yu J, Kinzler K, Vogelstein B, Williams J. Cell-cycle arrest versus cell death in cancer therapy. Nat. Med. 3: 1034-1036 (1997)

    Article  CAS  Google Scholar 

  • Wang G, Chan CH, Gao Y, Lin HK. Novel roles of Skp2 E3 ligase in cellular senescence, cancer progression, and metastasis. Chin. J. Cancer 31: 169-177 (2012)

    Article  Google Scholar 

  • Wang J, Lou P, Lesniewski R, Henkin J. Paclitaxel at ultra low concentrations inhibits angiogenesis without affecting cellular microtubule assembly. Anti-cancer Drugs 14: 13-19 (2003)

    Article  Google Scholar 

  • Wei Z, Jiang X, Liu F, Qiao H, Zhou B, Zhai B, Zhang L, Zhang X, Han L, Jiang H, Krissansen GW, Sun X. Downregulation of Skp2 inhibits the growth and metastasis of gastric cancer cells in vitro and in vivo. Tumour Biol. 34: 181-192 (2013)

    Article  CAS  Google Scholar 

  • Wen Y, Wang K, Yang K. Inhibiting the role of Skp2 suppresses cell proliferation and tumorigenesis of human gastric cancer cells via the upregulation of p27kip1. Mol. Med. Rep. 14: 3917-3924 (2016)

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This study was supported by the Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry, and Fisheries (IPET) through the High Value-added Food Technology Development Program, funded by the Ministry of Agriculture, Food, and Rural Affairs (MAFRA) (Grant No. 116010-03-1-CG000) and research fund from Chosun University, 2017.

Author information

Authors and Affiliations

  1. Bunong Seed Korea R&D Center, Gimje-si, Jeollabuk-do, 54324, Republic of Korea

    Woong Kim

  2. The Garden of Naturalsolution, Osan-si, Gyeonggi-do, 18103, Republic of Korea

    Cheolwoo Park

  3. Department of Biomedical Science, Chosun University, Gwangju, 61452, Republic of Korea

    Jaeyoung Park, Hyeonsook Cheong & Seok-Jun Kim

  4. BK21-Plus Research Team for Bioactive Control Technology, Chosun University, Gwangju, 61452, Republic of Korea

    Seok-Jun Kim

Authors
  1. Woong Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Cheolwoo Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jaeyoung Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hyeonsook Cheong
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Seok-Jun Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Seok-Jun Kim.

Ethics declarations

Conflict of interest

The authors have no conflicting interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 104 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kim, W., Park, C., Park, J. et al. Pine needle hexane extract promote cell cycle arrest and premature senescence via p27KIP1 upregulation gastric cancer cells. Food Sci Biotechnol 29, 845–853 (2020). https://doi.org/10.1007/s10068-019-00730-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10068-019-00730-5

Keywords

Search

Navigation