Olea europaea leaf extract suppress stemness-Characteristics of gastric cancer via long non-coding RNAs

Tekin C., Ercelik M., TEZCAN G., AKSOY M. S., EGELİ Ü., ÇEÇENER G., ...More

EUROPEAN JOURNAL OF INTEGRATIVE MEDICINE, vol.49, 2022 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 49
  • Publication Date: 2022
  • Doi Number: 10.1016/j.eujim.2022.102099
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, EMBASE
  • Keywords: Anticancer drug, Stem-like cancer cell, Gastric cancer, Long non-coding RNAs, Tumor sphere, CELLS, EXPRESSION, ADENOCARCINOMA, 5-FLUOROURACIL, FLUOROURACIL, METASTASIS, MECHANISMS, RESPONSES, EXPOSURE, PROMOTES
  • Bursa Uludag University Affiliated: Yes


Introduction: 5-Fluorouracil (5-FU) and Cisplatin (Cis) are insufficient to fight against stem-like cancer cell (CSC)-phenotype Gastric cancer (GC). Therefore, new therapeutic approaches are required to treat CSC-GC patients. Although the anticancer effect of Olea europaea leaf extract (OLE) has been described for multiple types of cancer, including GC, the potential of OLE to be used as a complementary to 5-FU and Cis to treat CSC-GC remains largely unknown. This study uniquely investigated the potential of OLE to be used as complementary to 5-FU-Cis therapy to alleviate the CSC-mediated aggressiveness of GC. Methods: The AGS cells, A GC cell line was treated with OLE-only and its combinations with 5-FU-Cis. Tumor aggressiveness, colony formation, and vascularization were analyzed using tumorsphere and clonogenic assays and ex-vivo analyses. In addition, their effect on the expression of CSC markers, including CD133, OCT4, NANOG, and SOX2 and LncRNA, PVT1, MALAT1, H19, and SNHG16, was investigated using RT-qPCR. Results: OLE-only and involvement of OLE to 5-FU+Cis treatment reduced the size of tumor-spheres (p < 0.0001), number of colonies (p < 0.0001), and vascularization. In addition, the OLE-5-FU-Cis combination decreased mRNA expression levels CSC markers and LncRNA, PVT1, H19, and SNHG16 expression levels compared to 5-FU+Cis (p < 0.05). Conclusion: OLE reduced the survival capacity of CSC phenotype cells by decreasing LncRNA PVT1, MALAT1, and H19 and facilitates the aggressive features of GC cells. Further analysis and validations are required; current findings suggest that OLE could be complementarily used to improve the effect of 5-FU+Cis therapy for GC.