Abstract LB-045: Iron depletion suppress the stemness markers and functions of cancer stem cells

Abstract

Abstract Background: Cancer stem cells (CSCs) have been proposed to be responsible for tumor initiating, drug resistance, metastasis, and recurrence. Although CSCs are considered to be important targets therapeutically, clinically effective CSC targeting strategies have not yet been established. Iron plays an important role in critical cellular processes, such as energy production and DNA synthesis. Although adequate iron levels are essential for human health, iron overload is known to cause some types of cancer. CSCs are considered to be involved in the tumor regardless of early stage. Thus we have focused on the relationship between iron and CSCs. We previously reported that the expression of stemness markers was suppressed by iron chelator in miPS and miPS inducible CSC model cells (miPS-LLCcm). Here, we hypothesized that the expression of stemness markers and function were also suppressed by iron chelator in high malignant cancer cells with stemness potential. Method: We used 4 stemness markers expressing cancer cell lines (HSC-2: Oral squamous cancer, TE-4 and OE33: Esophageal cancer, and NT-2: Embryonal cell carcinoma). Deferasirox (DFX), an oral iron chelator, was used. The stemness markers expression including Nanog, Sox2, Oct3/4, Klf-4 and c-Myc was examined by western blot analysis. Self-renewal ability was examined by sphere formation assay. Anti-proliferative effect of DFX was assessed combined with CDDP using HSC-2 cells. Result: DFX suppressed the expression of stemness markers and sphere formation ability in 4 cancer cell lines. In contrast, CDDP could not suppressed them. In HSC-2 cells, combination therapy with CDDP and DFX synergistically suppressed the proliferation with suppression of stemness markers. Conclusion: Our results indicated that iron depletion generally suppressed the stemness markers and functions of high malignant cells same as miPS and miPS-LLCcm. Thus iron depletion can be a novel therapy for CSCs via suppression of CSCs function. Citation Format: Toshiaki Ohara, Yuki Katsura, Kazuhiro Noma, Toru Narusaka, Takuya Kato, Hiroaki Sato, Satoshi Komoto, Yasuko Tomono, Takayuki Ninomiya, Hiroshi Tazawa, Shunsuke Kagawa, Yasuhiro Shirakawa, Toshiyoshi Fujiwara. Iron depletion suppress the stemness markers and functions of 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 LB-045.