ZFIN ID: ZDB-PUB-180214-9
Wogonin exacerbates the cytotoxic effect of oxaliplatin by inducing nitrosative stress and autophagy in human gastric cancer cells
Hong, Z.P., Wang, L.G., Wang, H.J., Ye, W.F., Wang, X.Z.
Date: 2018
Source: Phytomedicine : international journal of phytotherapy and phytopharmacology   39: 168-175 (Journal)
Registered Authors:
Keywords: Autophagy, Gastric cancer, Nitrosative stress, Oxaliplatin, Wogonin
MeSH Terms:
  • Animals
  • Antineoplastic Combined Chemotherapy Protocols/pharmacology*
  • Apoptosis/drug effects
  • Autophagy/drug effects
  • Cell Line, Tumor
  • Cell Survival/drug effects
  • Flavanones/administration & dosage
  • Humans
  • Membrane Potential, Mitochondrial/drug effects
  • Nitrosative Stress/drug effects
  • Organoplatinum Compounds/administration & dosage
  • Peroxynitrous Acid/metabolism
  • Stomach Neoplasms/drug therapy*
  • Stomach Neoplasms/pathology
  • Xenograft Model Antitumor Assays
  • Zebrafish
PubMed: 29433678 Full text @ Phytomedicine
ABSTRACT
Gastric cancer remains one of the leading cause of death in the world. Drug combinations are potential approaches to provide more efficient treatments that minimize side effects.
We investigated the pharmacological effects of the combination of wogonin with oxaliplatin on gastric cancer cells in vitro and in vivo.
In the present study, we found that wogonin enhanced the cytotoxicity of oxaliplatin; the drug combination resulted in strong synergistic inhibition of the cell viability in BGC-823 cells and in a zebrafish xenograft model. Interestingly, the combined treatment of wogonin and oxaliplatin modulated the expression of phospho-JNK (Thr183/Tyr185), phospho-ULK1 (Ser555) and the formation of LC3II. Confocal imaging data consistently showed that wogonin exacerbates the oxaliplatin-induced dissipation of the mitochondrial membrane potential (ΔΨm) and formation of peroxynitrite in BGC-823 cells. Moreover, wogonin allows a reduction in oxaliplatin dose when they are combined; therefore, it is a relevant strategy for reducing the side effects of oxaliplatin while achieving the same response.
These results suggest that wogonin can be a potential therapeutic candidate for enhancing the efficacy of oxaliplatin in gastric cancer treatment.
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