Ethanol extracts of Allium sp. regulate cyclooxygenase-2 and E-cadherin expression in gastric cancer MKN74 cell line and enhance doxorubicin toxicity

Abstract

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 is Allium genus, which includes garlic. The relationship between CDH1 and COX2 in GC cells treated with Allium species extract has never been evaluated. Methods In this study, the MKN28 and MKN74 GC cell lines were treated with ethanol extracts of Allium angulosum L., Allium lusitanicum Lam., Allium sativum L. (from Malaysia and Poland), Allium tibeticum Rendle and Allium ursinum L. 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 of A. sativum L. (Poland and Malaysia), A. tibeticum Rendle and A. ursinum L. 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 of Allium extract’s toxicity. In comparison to DOX, tested extracts were more toxic. Moreover, A. sativum revealed synergistic effect with the drug. Conclusion In conclusion, the results indicate the potential application of Allium genus to GC chemoprevention and treatment support through CDH restoration and COX2 downregulation. This issue needs further investigations as it might be used in clinics.

Hairy Garlic (Allium subhirsutum) from Sicily (Italy): LC-DAD-MSn Analysis of Secondary Metabolites and In Vitro Biological Properties

“…Many publications deal with allium species and their bioactivities, indicating significant interest by the scientific community on this natural product, especially in the area of cytotoxic and antitumor compounds. In this context, our data on A. subhirsutum represent new information showing moderate cytotoxic activity as previously reported [ 33 , 34 , 35 , 36 , 37 ].…”

The Potential Application of Allium Extracts in the Treatment of Gastrointestinal Cancers

“…Another advantage of garlic supplementation is the blockage of oxidative damage by the upregulation of reduced-glutathione (GSH)-dependent hepatic detoxification systems in experimental models [38]. Allium constituents also tend to induce the upregulation of cadherin-1 (CDH1) and cyclooxygenase 2 (COX-2) downregulation, further supporting the role of the Allium genus in gastric cancer chemoprevention [39]. Allium-derived flavonols, by inhibiting the PI3K/Akt signaling pathway, induce the apoptosis of gastric cancer cells in a caspase-dependent and mitochondria-mediated manner [40].…”

Inhibition or Reversal of the Epithelial-Mesenchymal Transition in Gastric Cancer: Pharmacological Approaches

“…In addition, the combination of doxorubicin and resveratrol synergistically enhanced caspase-3 and reduced vimentin and Ki-67 [ 89 ]. It was demonstrated that the combination of doxorubicin with Allium species might be beneficial in exerting toxic effects on GC cell lines by the restoration of CDH1 and COX2 downregulation [ 90 ].…”