Effects of heavy water (D2O) on human pancreatic tumor cells

Abstract. Background: Pancreatic cancer constitutes anentity which is difficult to treat and, therefore, mostly fatal.Since heavy water (deuterium oxide, D 2 O) was shown to beactive in various cancer cell lines in vitro and in vivo, we nowinvestigated its effects in human pancreatic tumor cells.Materials and Methods: The cytotoxic effects of D 2 O wereexamined in three pancreatic cancer cell lines (AsPC-1,BxPC-3 and PANC-1). Induction of apoptosis wasdetermined by Hoechst/propidium iodide double staining andcell cycle distribution was investigated by FACS analysis.Results: Employing a clonogenic assay, D 2 O yielded IC 50 values of 15%, 18% and 27% in AsPC-1, PANC-1 andBxPC-3 cells, respectively, and led to the induction ofapoptosis when compared to untreated controls. Moreover,D 2 O caused a cell cycle arrest in the G2-M-phase (BxPC-3,PANC-1) or in the S-phase (AsPC-1). Conclusion: It is hopedthat D 2 O might offer an additional option for the treatmentof pancreatic carcinomas. Pancreatic cancer occurs with an incidence of 2 to 10 per100,000 persons per year. Because of its unspecificsymptoms, it is often diagnosed in an extremely late phaseof the disease, mostly after formation of metastases.Therefore, therapy modalities are quite poor at the time ofdiagnosis. Only in less than 20% of patients, can pancreaticcarcinomas be removed by surgery. Individuals sufferingfrom inoperable tumors receive palliative therapy, includingchemotherapy and radiation therapy. However, thetreatment options are very limited and most patients diewithin months after diagnosis. Incubation of tumor cells with various concentrations ofD