Chrysophanol inhibits of colorectal cancer cell motility and energy metabolism by targeting the KITENIN/ErbB4 oncogenic complex

Varlı M., Kim E., Oh S., Pulat S., Zhou R., Gamage C. D. B., ...Daha Fazla

Cancer Cell International, cilt.24, sa.1, 2024 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 24 Sayı: 1
  • Basım Tarihi: 2024
  • Doi Numarası: 10.1186/s12935-024-03434-x
  • Dergi Adı: Cancer Cell International
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, Biotechnology Research Abstracts, EMBASE, Directory of Open Access Journals
  • Anahtar Kelimeler: Aerobic glycolysis, Anthraquinone, Chrysophanol, Colorectal cancer, ErbB4, KITENIN, Metastasis
  • Marmara Üniversitesi Adresli: Evet

Özet

Background: Expression of the KITENIN/ErbB4 oncogenic complex is associated with metastasis of colorectal cancer to distant organs and lymph nodes and is linked with poor prognosis and poor survival. Methods: Here, we used in vitro and in silico methods to test the ability of chrysophanol, a molecule of natural origin, to suppress the progression of colorectal cancer by targeting the KITENIN/ErbB4 complex. Results: Chrysophanol binds to ErbB4, disrupting the ErbB4/KITENIN complex and causing autophagic degradation of KITENIN. We demonstrated that chrysophanol binds to ErbB4 according to a molecular docking model. Chrysophanol reversed KITENIN-mediated effects on cell motility, aerobic glycolysis, and expression of downstream effector genes. Moreover, under conditions of KITENIN overexpression, chrysophanol suppressed the production of onco-metabolites. Conclusion: Chrysophanol suppresses oncogenic activities by targeting the KITENIN/ErbB4 complex. Graphical Abstract: (Figure presented.)