Alloimperatorin enhances chemosensitivity by modulating the c-MYC/NBS1 axis to induce sustained DNA damage

Shuting Han1, Jiaru Wang2, Jiao Xue1

  • 1School of Basic Medicine and Forensic Medicine, Baotou Medical College, Baotou, Inner Mongolia, 014040, China.

Insights

Alloimperatorin (Alloi) enhances gemcitabine (GEM) chemotherapy efficacy against tumors. This combination disrupts the c-MYC/NBS1 DNA repair pathway, improving cancer treatment outcomes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Chemoresistance remains a major challenge in cancer therapy.
  • TCM-derived small molecules targeting DNA repair pathways are underexplored.
  • Alloimperatorin (Alloi) shows anti-tumor potential, but its combination efficacy and mechanisms are unclear.

Purpose of the Study:

  • To investigate the efficacy and molecular mechanisms of Alloimperatorin (Alloi) combined with gemcitabine (GEM) in cancer treatment.
  • To evaluate the synergistic effects of the Alloi-GEM combination in vitro and in vivo.
  • To elucidate the underlying molecular pathways modulated by the Alloi-GEM regimen.

Main Methods:

  • In vitro and in vivo functional assays to assess synergistic effects.
  • Transcriptome sequencing and network pharmacology to identify key molecular targets.
  • Validation of identified targets using multiple molecular assays.

Main Results:

  • The Alloi-GEM combination demonstrated potent synergistic inhibition of tumor cell lines and pancreatic cancer progression in vivo.
  • Downregulation of c-MYC and Nijmegen Breakage Syndrome 1 gene (NBS1) was identified as a key mechanistic event.
  • The Alloi-GEM regimen induced sustained DNA damage by disrupting the c-MYC-NBS1 axis, impairing DNA damage response.

Conclusions:

  • Alloimperatorin (Alloi) sensitizes tumors to gemcitabine (GEM) chemotherapy.
  • The combination therapy functions by modulating the c-MYC/NBS1 axis, leading to enhanced DNA damage.
  • This Alloi-GEM combinatorial strategy presents a promising approach for improving cancer treatment efficacy.

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