Skip to content
2000
  1. Home
  2. A-Z Publications
  3. Protein and Peptide Letters
  4. Fast Track Articles
  5. Fast Track Article
image of Anti-Cancer Bioactive Peptide Induces Apoptosis in Gastric Cancer Cells through TP53 Signaling Cascade

Abstract

Introduction

Gastric cancer has emerged as one of the major diseases threatening human health. Our previous studies indicated that the anti-cancer bioactive peptide (ACBP) inhibits the initiation and progression of gastric cancer through apoptosis and cell cycle arrest, yet the mechanisms remain unclear. To elucidate the relationships between the effects of ACBP and the levels of cell differentiation, as well as the functional mechanisms of ACBP, we conducted a study using three human gastric cancer cell lines: NCI-N87, MGC-803, and another unspecified line.

Method

We investigated the impact of ACBP on the survival and morphology of these cancer cell lines, examined apoptosis and cell cycle progression, and detected the expression of TP53, TP63, and TP73 in cancer cells, as well as the expression of Bax, PUMA, and Mcl-1 in a xenograft mouse model. ACBP inhibited the proliferation of all three cancer cell lines in a dose-dependent manner, similar to the positive control and 5-fluorouracil (5-FU). The effect of ACBP correlated with the degree of differentiation of the cancer cells; the lower the differentiation degree, the stronger the inhibitory effect.

Result

After ACBP treatment, the expression of TP53, TP63, and TP73 increased in all cell lines. In the xenograft mouse model, ACBP inhibited the growth of MGC-803 cells . The apoptotic-related genes Bax and PUMA were upregulated, while Mcl-1 was downregulated. ACBP inhibited tumor cell growth by inducing apoptosis through the TP53 signaling cascade, upregulating TP53, TP63, and TP73 and their downstream apoptosis-promoting genes Bax and PUMA while downregulating the anti-apoptotic gene Mcl-1.

Conclusion

Notably, after ACBP treatment, Mcl-1 expression was significantly reduced in the tumor tissue of the xenograft model, indicating that ACBP induced apoptosis through the TP53 signaling cascade. This project provides a scientific basis for exploring the antitumor mechanism of ACBP in gastric cancer therapy.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/ppl/10.2174/0109298665350654250111144722
2025-02-10
2025-04-16

  • From This Site

    /content/journals/ppl/10.2174/0109298665350654250111144722
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. Chen C. Justo M. Gangi A. Hyperthermic intraperitoneal chemotherapy for gastric cancer: A narrative review. Chin. Clin. Oncol. 2023 12 6 68 10.21037/cco‑23‑90 38195075
    [Google Scholar]
  2. Furukawa K. Hatakeyama K. Terashima M. Nagashima T. Urakami K. Ohshima K. Notsu A. Sugino T. Yagi T. Fujiya K. Kamiya S. Hikage M. Tanizawa Y. Bando E. Kanai Y. Akiyama Y. Yamaguchi K. Molecular classification of gastric cancer predicts survival in patients undergoing radical gastrectomy based on project HOPE. Gastric Cancer 2022 25 1 138 148 10.1007/s10120‑021‑01242‑0 34476642
    [Google Scholar]
  3. Jemal A. Bray F. Center M.M. Ferlay J. Ward E. Forman D. Global cancer statistics. CA Cancer J. Clin. 2011 61 2 69 90 10.3322/caac.20107 21296855
    [Google Scholar]
  4. Kim Y.H. Kim J.H. Kim H. Kim H. Lee Y.C. Lee S.K. Shin S.K. Park J.C. Chung H.S. Park J.J. Youn Y.H. Park H. Noh S.H. Choi S.H. Is the recent WHO histological classification for gastric cancer helpful for application to endoscopic resection? Gastric Cancer 2016 19 3 869 875 10.1007/s10120‑015‑0538‑4 26324820
    [Google Scholar]
  5. Bray F. Laversanne M. Sung H. Ferlay J. Siegel R.L. Soerjomataram I. Jemal A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2024 74 3 229 263 10.3322/caac.21834 38572751
    [Google Scholar]
  6. Cui R. He J. Mei R. de Fromentel C.C. Martel-Planche G. Taniere P. Hainaut P. WITHDRAWN: Expression of p53, p63, and p73 isoforms in squamous cell carcinoma and adenocarcinoma of esophagus☆,☆☆. Biochem. Biophys. Res. Commun. 2005 336 1 339 345 10.1016/j.bbrc.2005.08.084 16126170
    [Google Scholar]
  7. Wang J. Pursell N.W. Samson M.E.S. Atoyan R. Ma A.W. Selmi A. Xu W. Cai X. Voi M. Savagner P. Lai C.J. Potential advantages of CUDC-101, a multitargeted HDAC, EGFR, and HER2 inhibitor, in treating drug resistance and preventing cancer cell migration and invasion. Mol. Cancer Ther. 2013 12 6 925 936 10.1158/1535‑7163.MCT‑12‑1045 23536719
    [Google Scholar]
  8. Yu L. Yang L. An W. Su X. Anticancer bioactive peptide-3 inhibits human gastric cancer growth by suppressing gastric cancer stem cells. J. Cell. Biochem. 2014 115 4 697 711 10.1002/jcb.24711 24214799
    [Google Scholar]
  9. Yanagisawa M. Yorozu K. Kurasawa M. Nakano K. Furugaki K. Yamashita Y. Mori K. Fujimoto-Ouchi K. Bevacizumab improves the delivery and efficacy of paclitaxel. Anticancer Drugs 2010 21 7 687 694 10.1097/CAD.0b013e32833b7598 20559127
    [Google Scholar]
  10. Li X. Wu H. Ouyang X. Zhang B. Su X. New bioactive peptide reduces the toxicity of chemotherapy drugs and increases drug sensitivity. Oncol. Rep. 2017 38 1 129 140 10.3892/or.2017.5674 28560442
    [Google Scholar]
  11. Su L. Xu G. Shen J. Tuo Y. Zhang X. Jia S. Chen Z. Su X. Anticancer bioactive peptide suppresses human gastric cancer growth through modulation of apoptosis and the cell cycle. Oncol. Rep. 2010 23 1 3 9 19956858
    [Google Scholar]
  12. Zhang L. Su X. Bioactive peptide inhibits acute myeloid leukemia cell proliferation by downregulating ALKBH5-mediated m6A demethylation of EIF4EBP1 and MLST8 mRNA. Cell Oncol. 2022 45 3 355 365 10.1007/s13402‑022‑00666‑9 35579750
    [Google Scholar]
  13. Li X. Xia L. Ouyang X. Suyila Q. Su L. Su X. Bioactive peptides sensitize cells to anticancer effects of oxaliplatin in human colorectal cancer xenografts in nude mice. Protein Pept. Lett. 2019 26 7 512 522 10.2174/0929866526666190405124955 30950338
    [Google Scholar]
  14. Chernousov A.F. Egorov A.V. Chernousov F.A. Levkin V.V. Vychuzhanin D.V. Kharlov N.S. Stepanov S.N. The use of Octreotide-depo for the pancreatitis’ prophylaxis after radical surgery of gastric cancer with lymphadenectomy. Khirurgiia (Mosk.) 2012 2012 8 39 43 22968556
    [Google Scholar]
  15. Shen Q. Wang H. Zhang L. TP63 functions as a tumor suppressor regulated by GAS5/miR-221-3p signaling axis in human non-small cell lung cancer cells. Cancer Manag. Res. 2023 15 217 231 10.2147/CMAR.S387781 36873253
    [Google Scholar]
  16. Xu Y. Li X. Su X. iTRAQ‑based proteomics analysis of the therapeutic effects of combined anticancer bioactive peptides and oxaliplatin on gastric cancer cells. Oncol. Rep. 2020 43 1 201 217 31746436
    [Google Scholar]
  17. Tong X. Zhuang Z. Wang X. Yang X. Bai L. Su L. Wei P. Su X. ACBP suppresses the proliferation, migration, and invasion of colorectal cancer via targeting Wnt/beta-catenin signaling pathway. Biomed. Pharmacother. 2021 137 111209 10.1016/j.biopha.2020.111209 33581651
    [Google Scholar]
  18. Su L. Shi Y. Yan M. Xi Y. Su X. Anticancer bioactive peptides suppress human colorectal tumor cell growth and induce apoptosis via modulating the PARP-p53-Mcl-1 signaling pathway. Acta Pharmacol. Sin. 2015 36 12 1514 1519 10.1038/aps.2015.80 26592508
    [Google Scholar]
  19. Wang Y.F. Yan M.R. Jia S.Q. Liu G.R. Su X.L. Influence of the PCNA and Caspase-8 expression of anti-cancer bioactive peptide on experimental gastric cancer. Acta Acad Med Nei Mongol 2009 31 6 9
    [Google Scholar]
  20. Su X. Dong C. Zhang J. Su L. Wang X. Cui H. Chen Z. Combination therapy of anti-cancer bioactive peptide with Cisplatin decreases chemotherapy dosing and toxicity to improve the quality of life in xenograft nude mice bearing human gastric cancer. Cell Biosci. 2014 4 1 7 10.1186/2045‑3701‑4‑7 24507386
    [Google Scholar]
  21. Jia S.Q. Wang W.L. Su X.L. Inhibitory effect of anti-cancer bioactive peptide on the proliferation of human breast cancer cell line nm231. Chin Med Biotechnol 2007 2 270 276
    [Google Scholar]
  22. Wen Z. Su X. Influence of p53 and Bcl-2 expression of anti-cancer bioactive peptide on experimental gastric cancer. Med Recapitulate 2011 17 1557 1559
    [Google Scholar]
  23. Hu D. Huang J.W. Hu S.P. Wang B. Gao L.Y. Expression and significance of the P53, P63 and P73 proteins in osteosarcoma. Chin J Bone Joint 2004 3 47 50
    [Google Scholar]
  24. Arcolino F.O. Ribeiro D.L. Gobbo M.G. Taboga S.R. Góes R.M. Proliferation and apoptotic rates and increased frequency of p63‐positive cells in the prostate acinar epithelium of alloxan‐induced diabetic rats. Int. J. Exp. Pathol. 2010 91 2 144 154 10.1111/j.1365‑2613.2009.00696.x 20041964
    [Google Scholar]
  25. Kaufmann O. Fietze E. Mengs J. Dietel M. Value of p63 and cytokeratin 5/6 as immunohistochemical markers for the differential diagnosis of poorly differentiated and undifferentiated carcinomas. Am. J. Clin. Pathol. 2001 116 6 823 830 10.1309/21TW‑2NDG‑JRK4‑PFJX 11764070
    [Google Scholar]
  26. Moreno J. Bahmad H. Aljamal A. Delgado R. Salami A. Guillot C. Castellano-Sánchez A. Medina A. Sriganeshan V. Prognostic significance of p53 and p63 in diffuse large b-cell lymphoma: A single-institution experience. Curr. Oncol. 2023 30 2 1314 1331 10.3390/curroncol30020102 36826063
    [Google Scholar]
  27. Schmale H. Bamberger C. A novel protein with strong homology to the tumor suppressor p53. Oncogene 1997 15 11 1363 1367 10.1038/sj.onc.1201500 9315105
    [Google Scholar]
  28. Rabow Z. Laubach K. Kong X. Shen T. Mohibi S. Zhang J. Fiehn O. Chen X. p73α1, an isoform of the p73 tumor suppressor, modulates lipid metabolism and cancer cell growth via stearoyl-coa desaturase-1. Cells 2022 11 16 2516 10.3390/cells11162516 36010592
    [Google Scholar]
  29. Foight G.W Locating herpesvirus Bcl-2 homologs in the specificity landscape of anti-apoptotic Bcl-2 proteins. Mol. Biol. 2015 427 15 2468 2490
    [Google Scholar]
  30. Zhang J. Huang K. O’Neill K.L. Pang X. Luo X. Bax/Bak activation in the absence of Bid, Bim, Puma, and p53. Cell Death Dis. 2016 7 6 e2266 10.1038/cddis.2016.167 27310874
    [Google Scholar]
  31. Liu Z. Ding Y. Ye N. Wild C. Chen H. Zhou J. Direct activation of bax protein for cancer therapy. Med. Res. Rev. 2016 36 2 313 341 10.1002/med.21379 26395559
    [Google Scholar]
  32. Dai H. Pang Y.P. Evaluation of the BH3-only protein puma as a direct Bak activator. Biol Chem. 2015 289 1 89 99 10.1371/journal.pone.0126645 26030884
    [Google Scholar]
  33. Papaianni E. El Maadidi S. Schejtman A. Phylogenetically distant viruses use the same BH3-only protein puma to trigger Bax/Bak-dependent apoptosis of infected mouse and human cells. PLoS One 2014 10 6 e0126645 10.3390/cells3020418 24814761
    [Google Scholar]
  34. Mojsa B. Lassot I. Desagher S. Mcl-1 ubiquitination: Unique regulation of an essential survival protein. Cells 2014 3 2 418 437 10.3390/cells3020418 24814761
    [Google Scholar]
/content/journals/ppl/10.2174/0109298665350654250111144722
Loading
Anti-Cancer Bioactive Peptide Induces Apoptosis in Gastric Cancer Cells through TP53 Signaling Cascade
Bentham Science Publishers ; https://doi.org/10.2174/0109298665350654250111144722
/content/journals/ppl/10.2174/0109298665350654250111144722
/content/journals/ppl/10.2174/0109298665350654250111144722
Loading

Data & Media loading...


  • Article Type:     Research Article
Keywords: TP53 signaling.10-Sep-2024 ; tumor suppressor gene ; human gastric cancer cells ; anti-cancer bioactive peptide ; differentiation ; Chemotherapy

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test