Abstract 159: Frankincense essential oil and doxorubicin treatment inhibited cell proliferation and induced apoptosis in CD133+ and CD90+ subpopulation hepatocellular carcinoma cancer stem cells

Abstract

Abstract Frankincense essential oil has been known in traditional medicine of many countries as wealth of health for the treatment of inflammatory diseases, anti-bacterial, anti-fungal activities, and might possess anti-cancer activities, based on their anti-proliferative and pro-apoptotic activities, but its anticancer role against cancer stem cells (CSC) in hepatocellular carcinoma (HCC) cell lines and the underlying molecular mechanisms remain uninvestigated. Doxorubicin is one of the efficient factors for HCC treatment, but the resistance to it is presenting a major obstacle for HCC treatment. The main aim of this study, isolated CD133+/CD90+ subpopulation from HCC cell line by flow cytometry, and evaluated the effects of Frankincense essential oil and Doxorubicin treatment on cell viability, colony formation, cellular proliferation, cell cycle distribution and apoptosis induction through DNA fragmentation of HCC cells and its isolated CD133+/CD90+ CSCs. Cell viability was monitored using an MTT assay. In addition, apoptosis induction was labeled by Annexin V-fluorescein isothiocyanate/propidium iodide and measured using flow cytometry. Western blotting was used to examine the protein expression of p53, Bcl-2, cyclin D1, and cleaved-caspases-3 and -9. Our results demonstrated that Frankincense essential oil or Doxorubicin suppressed the cell viability of CD133+/CD90+cells in a concentration-dependent manner after 24hrs of treatment. In addition, Frankincense essential oil or Doxorubicin induced a significant apoptosis induction in CD133+/CD90+ subpopulation cells through DNA fragmentation, caspase-9 and caspase-3 activation, increased the expression of pro-apoptotic proteins, including p53, decreased the protein level of anti-apoptotic protein Bcl-2, and regulated the expression of cell cycle regulators as cyclin D1. Levels of cyclin D1 expression were gradually suppressed by Frankincense essential oil in tested cells. Our data revealed that Frankincense essential oil has been shown to arrest cancer cells at the G1-phase of cell cycle, suppresses cyclin D1, and E, cdk 2, as well as increases expression of p21 through a p53-independent pathway. Furthermore, the Frankincense essential oil treatment strongly inhibited stemness characteristics of CSC subpopulation, colony formation and dramatically inhibited CD133+/CD90+ tumor growth in vitro. In conclusion, our results suggested that Frankincense essential oil and Doxorubicin may be a potential treatment for apoptosis induction in CSC and may provide an attractive therapeutic strategy against HCC. Citation Format: Amira S. Fyala, Ahmed S. Sultan. Frankincense essential oil and doxorubicin treatment inhibited cell proliferation and induced apoptosis in CD133+ and CD90+ subpopulation hepatocellular carcinoma cancer stem cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 159.