Abstract 4367: IP6: A potential novel therapy for cancer stem cells

Background and Aims: We recently discovered that inositol hexaphosphate (IP6), a new anticancer agent, killed malignant cancer stem cells (CSC) such as: CD133+, CD44+ and CD24+ cells via apoptotic pathways, but did not kill normal epithelial cells, fibroblasts, lymphocytes and macrophages. The effects of IP6 on malignant CSC have not been known. To clarify the molecular mechanism of IP6 destruction of CSC cells, we studied its effects in several CSC from malignant KS-Y1, B-NHL, prostate cancer (PCA) and breast cancer (BCA) cell lines. Methods and Results: CSC were isolated from KSY-1, B-NHL/HIV Tg26 mice, PCA and BCA cancer cell lines using magnetic beads conjugated with MoAbs and analyzed by flow cytometry for CD133, CD44 and CD24 cells. CSC cells were cultured using liquid and semisolid techniques for tumorigenesis assay and were treated with IP6 at doses of 100, 300 and 500 µg/ml, untreated (PBS) and control treatment with 10-100 µg/ml of Taxol. Cell viability was determined by trypan blue at 1 hr-24 hrs. FACS analyses were performed for apoptotic activities by detection of death molecules such as Annexin V-FITC and PI-CD95, and apoptosis assessed by 3D confocal microscopy. Significant killing of malignant CSC with IP6 in a dose-dependent manner were shown ex vivo in proliferation/differentiation tumorigenesis assay, in quantitative/qualitative FACS analyses and 3D confocal microscopy. In contrast, Taxol molecule with doses 10-100 µg/ml did not kill the CSC. Since it is known that CSC are resistant to Taxol treatment and radiation therapy, and IP6 significanly decreased proliferation and induced apoptosis in malignant and metastatic CSC, the results from our experiments suggest that IP6 may be an excellent new drug for treatment of CSC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4367. doi:10.1158/1538-7445.AM2011-4367