Ethanol extracts ofsp. regulate cyclooxygenase-2 and E-cadherin expression in gastric cancer MKN74 cell line and enhance doxorubicin toxicity.
Food Nutr Res. 2019 ;63. Epub 2019 Jun 25. PMID: 31297043
Background: Gastric cancer (GC) remains one of the leading causes of cancer-related death. Its aetiology is multifactorial, but the major risk factor is a high in salt diet. During gastric carcinogenesis, cadherin-1 (CDH1) down-expression and cyclooxygenase 2 (COX2) overexpression may be observed. The intensity of these alterations contributes to the GC invasion, its metastases and poor prognosis. As the diet plays a significant role in the aetiology of GC, it is reasonable to include the nutritional chemoprevention agents. One of the plant genus demonstrating chemoprotective properties isgenus, which includes garlic. The relationship between CDH1 and COX2 in GC cells treated withspecies extract has never been evaluated.
Methods: In this study, the MKN28 and MKN74 GC cell lines were treated with ethanol extracts ofL.,Lam.,L. (from Malaysia and Poland),Rendle andL. The cytotoxicity of the extracts and their influence on COX2 and CDH1 mRNA and protein expression were evaluated as well as their influence on doxorubicin's (DOX) efficacy - a drug that has been used in GC treatment.
Results: Among the tested species, ethanol extracts ofL. (Poland and Malaysia),Rendle andL. influenced the levels of CDH1 and COX2, but only in the MKN74 cell line. Thus, it is possible that tumours with increased COX2 expression will be more susceptible to garlic treatment. Observed phenomenon was independent ofextract's toxicity. In comparison to DOX, tested extracts were more toxic. Moreover,revealed synergistic effect with the drug.
Conclusion: In conclusion, the results indicate the potential application ofgenus to GC chemoprevention and treatment support through CDH restoration and COX2 downregulation. This issue needs further investigations as it might be used in clinics.