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Phytomedicine. 2018 Jan 15;39:168-175. doi: 10.1016/j.phymed.2017.12.019. Epub 2017 Dec 18.

Wogonin exacerbates the cytotoxic effect of oxaliplatin by inducing nitrosative stress and autophagy in human gastric cancer cells.

Author information

1
Department of Tumor Surgery, Chifeng Municipal Hospital, Chifeng Clinical Medical School of Inner Mongolia Medical University, Chifeng, China.
2
Department of Pharmacy, The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
3
Department of Pharmacy, The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China. Electronic address: yeweifeng@zju.edu.cn.
4
Department of Tumor Surgery, Chifeng Municipal Hospital, Chifeng Clinical Medical School of Inner Mongolia Medical University, Chifeng, China. Electronic address: wangxz@cfhospital.com.cn.

Abstract

BACKGROUND:

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.

PURPOSE:

We investigated the pharmacological effects of the combination of wogonin with oxaliplatin on gastric cancer cells in vitro and in vivo.

METHODS AND RESULTS:

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.

CONCLUSION:

These results suggest that wogonin can be a potential therapeutic candidate for enhancing the efficacy of oxaliplatin in gastric cancer treatment.

KEYWORDS:

Autophagy; Gastric cancer; Nitrosative stress; Oxaliplatin; Wogonin

PMID:
29433678
DOI:
10.1016/j.phymed.2017.12.019
[Indexed for MEDLINE]

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