Skip to main content
SpringerLink
Log in

Dehydroabietic acid inhibits the gastric cancer cell growth via induced apoptosis and cell cycle arrest

  • Original Article
  • Published:
Molecular & Cellular Toxicology Aims and scope Submit manuscript

Abstract

Background

Gastric cancer is one of the serious malignant tumors with high incidence worldwide. The two commonly used treatment strategies for gastric cancer include chemotherapy and radiation therapy. Conventional anticancer drugs have limited effectiveness. Therefore, it is important to explore new anticancer drugs. Dehydroabietic acid (DAA) is known to have anti-bacterial, anti-inflammatory, and anticancer effects. However, there are fewer reports on the effect of DAA on human gastric cancer cell lines.

Objective

We investigated the gastric cell growth inhibitory effects of DAA on human gastric cancer cell lines. Gastric cancer cell proliferation, apoptosis and cell cycle arrest assay were detected by WST assay, crystal violet staining assay, Flow cytometry, RT-PCR and western blot analysis.

Results

These results showed that as the concentration of DAA increased, the proliferation inhibitory effect appeared in gastric cancer cells. In addition, DAA induced sub-G1 phase accumulation and G1 cell cycle arrest, and subsequently induced apoptosis in AGS and YCC-2 cells. In addition, the expression of the pro-apoptotic Bax was upregulated, and that of the anti-apoptotic Bcl-2 was downregulated in DAA-treated AGS and YCC-2 cells. Moreover, DAA induced the cleavage of caspase-3 and PARP.

Conclusion

These results suggest that DAA induces cell death through mitochondria-mediated apoptosis and G1 cell cycle arrest. Therefore, our results indicate the anticancer and therapeutic potential of DAA for treatment of human gastric cancer.

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

Similar content being viewed by others

References

  • Bailon-Moscoso N, Cevallos-Solorzano G, Romero-Benavides JC, Orellana MI (2017) Natural compounds as modulators of cell cycle arrest: application for anticancer chemotherapies. Curr Genom 18:106–131

    Article  CAS  Google Scholar 

  • Besson A, Dowdy SF, Roberts JM (2008) CDK inhibitors: cell cycle regulators and beyond. Dev Cell 14:159–169

    Article  CAS  Google Scholar 

  • Danial NN (2007) BCL-2 family proteins: critical checkpoints of apoptotic cell death. Clin Cancer Res 13:7254–7263

    Article  CAS  Google Scholar 

  • Frenzel A, Grespi F, Chmelewskij W, Villunger A (2009) Bcl2 family proteins in carcinogenesis and the treatment of cancer. Apoptosis 14:584–596

    Article  CAS  Google Scholar 

  • Fulda S, Debatin KM (2006) Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy. Oncogene 25:4798–4811

    Article  CAS  Google Scholar 

  • Gim J, Kim HS, Kim J, Choi M, Kim JR, Chung YJ, Cho KH (2010) A system-level investigation into the cellular toxic response mechanism mediated by AhR signal transduction pathway. Bioinformatics 26:2169–2175

    Article  CAS  Google Scholar 

  • Hosseini A, Ghorbani A (2015) Cancer therapy with phytochemicals: evidence from clinical studies. Avicenna J Phytomed 5:84–97

    CAS  PubMed  PubMed Central  Google Scholar 

  • Jiang X, Wang X (2004) Cytochrome C-mediated apoptosis. Annu Rev Biochem 73:87–106

    Article  CAS  Google Scholar 

  • Jung KW, Won YJ, Kong HJ, Lee ES, Community of Population-Based Regional Cancer R (2018) Cancer statistics in Korea: incidence, mortality, survival, and prevalence in 2015. Cancer Res Treat 50:303–316

    Article  Google Scholar 

  • Kamb A (1995) Cell-cycle regulators and cancer. Trends Genet 11:136–140

    Article  CAS  Google Scholar 

  • Kang HG, Kim WJ, Kang HG, Chun KH, Kim SJ (2020) Galectin-3 interacts with C/EBPbeta and upregulates hyaluronan-mediated motility receptor expression in gastric cancer. Mol Cancer Res 18:403–413

    Article  CAS  Google Scholar 

  • Kim R, Tanabe K, Uchida Y, Emi M, Inoue H, Toge T (2002) Current status of the molecular mechanisms of anticancer drug-induced apoptosis. The contribution of molecular-level analysis to cancer chemotherapy. Cancer Chemother Pharmacol 50:343–352

    Article  CAS  Google Scholar 

  • Krukiewicz K, Zak JK (2016) Biomaterial-based regional chemotherapy: Local anticancer drug delivery to enhance chemotherapy and minimize its side-effects. Mater Sci Eng C Mater Biol Appl 62:927–942

    Article  CAS  Google Scholar 

  • Kweon SS (2018) Updates on cancer epidemiology in Korea, 2018. Chonnam Med J 54:90–100

    Article  Google Scholar 

  • Li P, Nijhawan D, Budihardjo I, Srinivasula SM, Ahmad M, Alnemri ES, Wang X (1997) Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell 91:479–489

    Article  CAS  Google Scholar 

  • Lim S, Kaldis P (2013) Cdks, cyclins and CKIs: roles beyond cell cycle regulation. Development 140:3079–3093

    Article  CAS  Google Scholar 

  • Lowe SW, Lin AW (2000) Apoptosis in cancer. Carcinogenesis 21:485–495

    Article  CAS  Google Scholar 

  • Luo D, Ni Q, Ji A, Gu W, Wu J, Jiang C (2016) Dehydroabietic acid derivative QC4 induces gastric cancer cell death via oncosis and apoptosis. Biomed Res Int 2016:2581061

    PubMed  PubMed Central  Google Scholar 

  • Pfeffer CM, Singh ATK (2018) Apoptosis: a target for anticancer therapy. Int J Mol Sci 19

  • Porter AG, Janicke RU (1999) Emerging roles of caspase-3 in apoptosis. Cell Death Differ 6:99–104

    Article  CAS  Google Scholar 

  • Senderowicz AM (2002) The cell cycle as a target for cancer therapy: basic and clinical findings with the small molecule inhibitors flavopiridol and UCN-01. Oncologist 7(3):12–19

    Article  CAS  Google Scholar 

  • Siegel RL, Miller KD, Jemal A (2018) Cancer statistics, 2018. CA Cancer J Clin 68:7–30

  • Sitarz R, Skierucha M, Mielko J, Offerhaus GJA, Maciejewski R, Polkowski WP (2018) Gastric cancer: epidemiology, prevention, classification, and treatment. Cancer Manag Res 10:239–248

    Article  CAS  Google Scholar 

  • Thoppil RJ, Bishayee A (2011) Terpenoids as potential chemopreventive and therapeutic agents in liver cancer. World J Hepatol 3:228–249

    Article  Google Scholar 

  • Wang IK, Lin-Shiau SY, Lin JK (1999) Induction of apoptosis by apigenin and related flavonoids through cytochrome c release and activation of caspase-9 and caspase-3 in leukaemia HL-60 cells. Eur J Cancer 35:1517–1525

    Article  CAS  Google Scholar 

  • Yip KW, Reed JC (2008) Bcl-2 family proteins and cancer. Oncogene 27:6398–6406

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This study was supported by the Chosun University in 2020.

Author information

Authors and Affiliations

  1. Department of Integrative Biological Sciences and BK21 FOUR Educational Research Group for Age-Associated Disorder Control Technology, Chosun University, Gwangju, 61452, Republic of Korea

    Won-Jin Kim, Hyeon-Gu Kang & Seok-Jun Kim

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

    Seok-Jun Kim

Authors
  1. Won-Jin Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hyeon-Gu Kang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Seok-Jun Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conception, design and funding: SJK; isolation, identification, experiments: WJK and HGK; writing the manuscript: WJK and SJK; reviewed the manuscript: all the authors.

Corresponding author

Correspondence to Seok-Jun Kim.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest.

Ethical approval

This article did not contain studies of human tissues and animals that required experimental permission, and institutional and national guidelines were also performed in this study.

Additional information

Publisher's Note

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kim, WJ., Kang, HG. & Kim, SJ. Dehydroabietic acid inhibits the gastric cancer cell growth via induced apoptosis and cell cycle arrest. Mol. Cell. Toxicol. 17, 133–139 (2021). https://doi.org/10.1007/s13273-021-00118-9

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13273-021-00118-9

Keywords

Search

Navigation