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. 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. 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. Our findings provide valuable insights into single and combinatorial effects of 7‑geranyloxycoumarin on the GA cells.

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