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Published on: May 10, 2024
7-geranyloxycoumarin enhanced radiotherapy effects on human gastric adenocarcinoma cells
Jebraeel Movaffagh1, Hamide Salari1, Elahe Merajifar2
1Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Background:
Gastric adenocarcinoma (GA) is a serious malignancy with growing incidence and mortality rate worldwide. The objective of the present study was to determine whether 7-geranyloxycoumarin, a natural monoterpene coumarin, could induce anticancer effects, in single use and/or in combination with anticancer drugs and ionizing radiation, on GA cells.
Materials And Methods:
7-geranyloxycoumarin was synthesized by a reaction between 7-hydroxycoumarin and transgeranyl bromide. MKN45 cells were treated with 7-geranyloxycoumarin, and the viability of cells was determined by resazurin. Apoptosis was then evaluated by flow cytometric analysis using annexin V and propidium iodide, and the expression of P53 and BCL2 was analyzed by quantitative polymerase chain reaction (qPCR). Combinatorial effects of 7-geranyloxycoumarin with 5-fluorouracil (5-FU), cisplatin (CDDP), and X radiation were also evaluated.
Results:
Assessment of cell viability indicated that 7-geranyloxycoumarin induced its toxic effects in a time- and dose-dependent manner. This was confirmed by the detection of apoptotic cells, and qPCR results revealed a significant downregulation in BCL2 expression. Although combinatorial use of 7-geranyloxycoumarin + 5-FU or + CDDP did not improve cytotoxicity of anticancer drugs, significant increase in the effectiveness of applied radiations was detected upon pretreatment with 7-geranyloxycoumarin.
Conclusion:
Our findings provide valuable insights into single and combinatorial effects of 7-geranyloxycoumarin on the GA cells.

