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7-geranyloxycoumarin enhanced radiotherapy effects on human gastric adenocarcinoma cells
Jebraeel Movaffagh1, Hamide Salari1, Elahe Merajifar2, Hamid Gholamhosseinian3, Azadeh Shahroodi1, Mehrdad Iranshahi4, Fatemeh B Rassouli5
1 Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
2 Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran
3 Department of Medical Physics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
4 Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
5 Novel Diagnostics and Therapeutics Research Group, Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran
Correspondence Address:
Fatemeh B Rassouli,
Novel Diagnostics and Therapeutics Research Group, Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad
Iran
 Source of Support: None, Conflict of Interest: None DOI: 10.4103/jcrt.jcrt_701_21
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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.
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