Skip to main content
SpringerLink
Log in

CS-NO suppresses inhibits glycolysis and gastric cancer progression through regulating YAP/TAZ signaling pathway

  • Original Paper
  • Published:
Cell Biochemistry and Biophysics Aims and scope Submit manuscript

Abstract

Context

Gastric cancer (GC) is a significant contributor to global mortality and is recognized for its elevated prevalence and fatality rates. Nitric Oxide (NO) plays a role in multiple aspects of cancer metastasis and progression. CS-NO is a polysaccharide-based biomaterial with NO-releasing properties that shows promising therapeutic potential. Nonetheless, the action mechanism of CS-NO in GC is still largely unclear.

Methods

The present study employed various experimental techniques, including CCK-8 assay, colony formation assay, EdU staining, and transwell assays, to evaluate the proliferation, migration, and invasion of GC cells. Additionally, ELISA was utilized to measure glucose uptake, lactate production, and cellular ATP levels in GC cells. In vivo investigations on nude mice were conducted to validate the in vitro results.

Objective

The present study aimed to examine the potential anti-tumor properties of CS-NO on GC through in vitro and in vivo investigations, while also exploring the underlying mechanisms involved.

Results

Our data suggested that CS-NO might prevent GC cell invasion and migration. Decreased expressions of GLUT1, HK2, and LDHA further demonstrated that CS-NO significantly suppressed aerobic glycolysis in GC cells. The administration of CS-NO resulted in a significant reduction of YAP and TAZ levels in GC cells. Our data further show that CS-NO treatment could inhibit GC cancer growth in mice, consistent with the significant decrease in Ki67, GLUT1 and YAP expression levels.

Discussion and conclusion

These findings could reveal the good effects of CS-NO therapy on inhibiting GC.

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

Data availability

All data generated or analysed during this study are included in this published article.

References

  1. Norwood, D. A., Montalvan, E. E., Dominguez, R. L., & Morgan, D. R. (2022). Gastric Cancer: Emerging Trends in Prevention, Diagnosis, and Treatment. Gastroenterology Clinics North America, 51(3), 501–518.

    Article  Google Scholar 

  2. Machlowska, J., & Baj, J. (2020). Gastric Cancer: Epidemiology, Risk Factors, Classification, Genomic Characteristics and Treatment Strategies. International Journal of Molecular Sciences, 21(11), 4012.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Messina, B., & Lo Sardo, F. (2023). Hippo pathway dysregulation in gastric cancer: from Helicobacter pylori infection to tumor promotion and progression. Cell Death Dis, 14(1), 21.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Lunardi, V. B., Soetaredjo, F. E., Putro, J. N., Santoso, S. P., Yuliana, M., Sunarso, J., Ju, Y. H., & Ismadji, S. (2021). Nanocelluloses: Sources, Pretreatment, Isolations, Modification, and Its Application as the Drug Carriers. Polymers, 13(13), 2052.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Fukumura, D., Kashiwagi, S., & Jain, R. K. (2006). The role of nitric oxide in tumour progression. Nature Reviews Cancer, 6(7), 521–534. eng.

    Article  CAS  PubMed  Google Scholar 

  6. Leung, E. L., Fraser, M., Fiscus, R. R., & Tsang, B. K. (2008). Cisplatin alters nitric oxide synthase levels in human ovarian cancer cells: involvement in p53 regulation and cisplatin resistance. British Journal of Cancer, 98(11), 1803–1809. eng.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Zhang, Y. Z., Wang, C. F., & Zhang, L. F. (2018). Cucurbitacin D impedes gastric cancer cell survival via activation of the iNOS/NO and inhibition of the Akt signalling pathway. Oncology Reports, 39(6), 2595–2603. eng.

    CAS  PubMed  PubMed Central  Google Scholar 

  8. de Oliveira, G. A., Cheng, R. Y. S., Ridnour, L. A., Basudhar, D., Somasundaram, V., McVicar, D. W., Monteiro, H. P., & Wink, D. A. (2017). Inducible Nitric Oxide Synthase in the Carcinogenesis of Gastrointestinal Cancers. Antioxidants & Redox Signaling, 26(18), 1059–1077.

    Article  Google Scholar 

  9. Yagihashi, N., Kasajima, H., Sugai, S., Matsumoto, K., Ebina, Y., Morita, T., Murakami, T., & Yagihashi, S. (2000). Increased in situ expression of nitric oxide synthase in human colorectal cancer. Virchows Archiv: an international Journal of Pathology, 436(2), 109–114.

    Article  CAS  PubMed  Google Scholar 

  10. Chazotte-Aubert, L., Pluquet, O., Hainaut, P., & Ohshima, H. (2001). Nitric oxide prevents gamma-radiation-induced cell cycle arrest by impairing p53 function in MCF-7 cells. Biochemical and Biophysical Research Communications, 281(3), 766–771.

    Article  CAS  PubMed  Google Scholar 

  11. Ziche, M., & Morbidelli, L. (2000). Nitric oxide and angiogenesis. Journal of Neuro-oncology, 50(1-2), 139–148.

    Article  CAS  PubMed  Google Scholar 

  12. Zhao, Q., Zhang, J., Song, L., Ji, Q., Yao, Y., Cui, Y., Shen, J., Wang, P. G., & Kong, D. (2013). Polysaccharide-based biomaterials with on-demand nitric oxide releasing property regulated by enzyme catalysis. Biomaterials., 34(33), 8450–8458.

    Article  CAS  PubMed  Google Scholar 

  13. Zhou, P., Cheng, S. W., Yang, R., Wang, B., & Liu, J. (2012). Combination chemoprevention: future direction of colorectal cancer prevention. European Journal of Cancer Prevention: the official journal of the European Cancer Prevention Organisation, 21(3), 231–240.

    Article  CAS  Google Scholar 

  14. Li, C., Anuraga, G., Chang, C., Weng, T., Hsu, H., Ta, H., Su, P., Chiu, P., Yang, S., & Chen, F., et al. (2023). Repurposing nitric oxide donating drugs in cancer therapy through immune modulation. Journal of Experimental & Clinical Cancer Research: CR, 42(1), 22.

    Article  CAS  PubMed Central  Google Scholar 

  15. Kumar, S., Kulkarni, R., & Sen, S. (2016). Cell motility and ECM proteolysis regulate tumor growth and tumor relapse by altering the fraction of cancer stem cells and their spatial scattering. Physical Biology, 13(3), 036001.

    Article  PubMed  Google Scholar 

  16. Roth, K. G., Mambetsariev, I., Kulkarni, P., & Salgia, R. (2020). The Mitochondrion as an Emerging Therapeutic Target in Cancer. Trends in Molecular Medicine, 26(1), 119–134. eng.

    Article  CAS  PubMed  Google Scholar 

  17. Ferreira, L. M. (2010). Cancer metabolism: the Warburg effect today. Experimental and Molecular Pathology, 89(3), 372–380. eng.

    Article  CAS  PubMed  Google Scholar 

  18. Muntane, J., De la Rosa, A. J., Marin, L. M., & Padillo, F. J. (2013). Nitric oxide and cell death in liver cancer cells. Mitochondrion., 13(3), 257–262.

    Article  CAS  PubMed  Google Scholar 

  19. Moya, I. M., & Halder, G. (2019). Hippo-YAP/TAZ signalling in organ regeneration and regenerative medicine. Nat Rev Mol Cell Biol, 20(4), 211–226.

    Article  CAS  PubMed  Google Scholar 

  20. Hasegawa, K., & Fujii, S. (2021). YAP signaling induces PIEZO1 to promote oral squamous cell carcinoma cell proliferation. The Journal of pathology, 253(1), 80–93.

    Article  CAS  PubMed  Google Scholar 

  21. Gao, R., Kalathur, R. K. R., Coto-Llerena, M., & Ercan, C. (2021). YAP/TAZ and ATF4 drive resistance to Sorafenib in hepatocellular carcinoma by preventing ferroptosis. EMBO molecular medicine, 13(12), e14351.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Wang, Z., Wang, F., Ding, X. Y., Li, T. E., Wang, H. Y., Gao, Y. H., Wang, W. J., Liu, Y. F., Chen, X. S., & Shen, K. W. (2022). Hippo/YAP signaling choreographs the tumor immune microenvironment to promote triple negative breast cancer progression via TAZ/IL-34 axis. Cancer Letters, 527, 174–190. eng.

    Article  CAS  PubMed  Google Scholar 

  23. Wang, D., Li, Z., Li, X., Yan, C., Yang, H., Zhuang, T., Wang, X., Zang, Y., Liu, Z., & Wang, T. et al. (2022). DUB1 suppresses Hippo signaling by modulating TAZ protein expression in gastric cancer. J Exp Clin Cancer Res, 41(1), 219.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Cordenonsi, M., Zanconato, F., Azzolin, L., Forcato, M., Rosato, A., Frasson, C., Inui, M., Montagner, M., Parenti, A. R., & Poletti, A., et al. (2011). The Hippo transducer TAZ confers cancer stem cell-related traits on breast cancer cells. Cell., 147(4), 759–772. eng.

    Article  CAS  PubMed  Google Scholar 

  25. Zhou, Y., Wang, Y., Zhou, W., Chen, T., Wu, Q., Chutturghoon, V. K., Lin, B., Geng, L., Yang, Z., & Zhou, L., et al. (2019). YAP promotes multi-drug resistance and inhibits autophagy-related cell death in hepatocellular carcinoma via the RAC1-ROS-mTOR pathway. Cancer Cell International, 19, 179 eng.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Koo, J. H., & Guan, K. L. (2018). Interplay between YAP/TAZ and Metabolism. Cell Metabolism, 28(2), 196–206. eng.

    Article  CAS  PubMed  Google Scholar 

Download references

Author contributions

Research idea and study design: N.G., H.M. and Y.S.; data acquisition: N.G., H.M.; data analysis/interpretation: D.L., H.F.; statistical analysis: C.S.; All authors read and approved the final manuscript.

Author information

Author notes

  1. These authors contributed equally: Na Guo, Hongxuan Ma

Authors and Affiliations

  1. The Second Oncology Department, Hebei Province Hospital of Chinese Medicine, Shijiazhuang, Hebei Province, China

    Na Guo, Dehui Li, Huanfang Fan & Chunxia Sun

  2. Faculty of Medicine, Faculty of Health and Behavioural Sciences, The University of Queensland, Brisbane, QLD, Australia

    Hongxuan Ma

  3. The Second Surgical Department, Hebei Province Hospital of Chinese Medicine, Shijiazhuang, Hebei Province, China

    Yunchao Sun

Authors
  1. Na Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hongxuan Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dehui Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Huanfang Fan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Chunxia Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yunchao Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yunchao Sun.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Ethics approval

The ethical standards of the study were approved by the Hebei Province Hospital of Chinese Medicine.

Additional information

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

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Guo, N., Ma, H., Li, D. et al. CS-NO suppresses inhibits glycolysis and gastric cancer progression through regulating YAP/TAZ signaling pathway. Cell Biochem Biophys 81, 561–567 (2023). https://doi.org/10.1007/s12013-023-01153-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12013-023-01153-0

Keywords

Search

Navigation