Abstract 2140: Assessment of curcumin-induced apoptosis and detection of cancer stem cell-like subpopulations in human esophageal cancer cell lines

Abstract

Abstract Curcumin, the major active ingredient of turmeric, has been shown to kill several types of malignant cells while it has little or no effect on normal cells, suggesting that it may be an effective therapeutic agent. Although some studies have investigated curcumin effects on esophageal cancer cell lines, no studies have characterized the curcumin-surviving cells, an important population that might show resistance to curcumin. There is increasing evidence that many cancers contain subpopulations that display stem cell characteristics. Cancer stem cells (CSCs) appear to play a central role in tumorigenesis, recurrence, metastasis, and resistance to cancer therapy. The aims of the current study were to assess curcumin-induced cell death and detect CSC subpopulations in six human esophageal cancer cell lines (TE-1, TE-8, KY-5, KY-10, YES-1, and YES-2). Aldehyde dehydrogenase-1A1 (ALDH1A1) expression was used as one marker for CSCs. To evaluate curcumin effects, the cell lines were exposed to 20-80 µM of curcumin for 30 hrs. In all six lines, cell death increased continuously with increasing dosage of curcumin based on a standard crystal violet assay. No cells survived at 80 µM, and the range of cell death across the six cell lines was 66 to 89% at 60 µM. To characterize the progeny of cells that survived curcumin, 1×105 cells from each line were exposed to 40-60 µM curcumin for 30 hours, and the colonies that formed from surviving cells were counted. The number of colonies present after 60 µM treatment varied between the cell lines (ranging from 8 to more than one hundred). The Yes-2 cell line did not survive at 60 µM, but produced 15 colonies after 40 µM treatment. Staining with an antibody against ALDH1A1 was used to compare CSC-like subpopulations within and among the original cells lines as well as cell lines established from the curcumin-treated lines. All cell lines were heterogeneous with respect to ALDH1A1 staining, revealing two subpopulations within each line. The intensity of staining was at least two times higher in the population considered to be CSCs. Interestingly, the curcumin-surviving cell lines showed a significant loss in the high-staining population compared to the untreated cells (T-test, p<0.05), suggesting that curcumin not only can kill cancer cells but also CSCs. Thus, esophageal CSCs appear to be highly sensitive to curcumin. Therefore, curcumin may be a more effective compound for esophageal cancer therapy than other chemotherapeutic agents. 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 2140. doi:10.1158/1538-7445.AM2011-2140