• Transcriptomic evidence reveals anticancer effects of xanthohumol in a homospheroid model of cancer cells
  • Zohreh Gholizadeh Siahmazgi,1 Shiva Irani,2 Parviz Fallah,3 Asal Ansari Pour,4 Hilda Samimi,5 Vahid Haghpanah,6,*
    1. Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
    2. Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
    3. Laboratory Science Department, Allied Medicine Faculty, Alborz University of Medical Sciences, Karaj, Iran
    4. University of Nicosia, Medical School, Nicosia, Cyprus
    5. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
    6. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran


  • Introduction: Humulus lupulus is one of the native plants of Iran that grows in the Northern provinces. Xanthohumol (XN) is the most important bioactive compound of Humulus lupulus, which has many uses in medicine. In this study, for the first time, the effect of XN in reducing the expression of resistance genes (MDR1and ABCG2 genes) in breast and lung cancer cells was investigated in three-dimensional (3D) cell culture.
  • Methods: XN from Humulus lupulus was purified using preparative-TLC method and confirmed by FT-IR and H-NMR methods. Spheroids of breast cancer (MCF-7) and lung cancer (A549) cell lines were prepared by drop hanging method. IC50 of XN was determined by MTT assay. Then expression of MDR1and ABCG2 genes were evaluated by qRT-PCR technique in 3D cell culture conditions under treatment with XN. The effect of XN on the cell cycle and apoptosis of cells treated by annexin kit were checked.
  • Results: The IC50 of XN was determined under 3D condition of MCF-7 and A549 cell lines, 12.37 μM and 31.17 μM, respectively. Treatment of cells with IC50 in 3D culture could significantly increase the sub-G1 phase in the cell cycle and apoptosis in both cell lines. Also, XN was able to significantly decrease the expression of ABCG2 and MDR1 genes in A549 cell line P < .01 and also significantly decrease (P < .01) MDR1 gene expression and ABCG2 gene expression in MCF-7 cell line (P < 0.05).
  • Conclusion: According to the obtained preliminary results in this study and by performing additional tests in the future, XN can be introduced as a natural compound in reducing the resistance of cancer cells.
  • Keywords: Xanthohumol, 3D cell culture, Resistance genes, Anticancer agents