Background: The aminosulfoacid derivative taurolidine was originally developed as an antibacterial substance. Recently, taurolidine was shown to exhibit antineoplastic effects both in vitro and in animal models via inhibition of protein synthesis, induction of apoptosis, and prevention of neoangiogenesis. In contrast to other antineoplastic agents, it has a strikingly favorable toxicity profile: It impairs neither liver and kidney function nor hematopoiesis. We investigated the effect of taurolidine in pancreatic cancer, a disease where therapeutic options are scarce.Methods: Two moderately differentiated ductal pancreatic adenocarcinoma cell lines were investigated: DSL-6A (murine) and HPAF-2 (human). Cells were incubated for 72 hours with increasing concentrations of taurolidine (0-2000 µmol/L), gemcitabine (0-100 µmol/L), or a combination of taurolidine (100 µmol/L) and gemcitabine in either high or low concentration. Cell proliferation and viability were assessed using a hemocytometer for direct cell counting and an MTT assay.Results: Both taurolidine and gemcitabine monotherapy inhibited cell growth and viability in a dose-dependent way. The highest concentrations analyzed inhibited cell proliferation by more than 98%. Taurolidine was no less effective than gemcitabine. In combination therapy, taurolidine was able to enhance efficacy of even high dose gemcitabine (Table). Similar results were achieved for cell viability.Conclusion: In pancreatic cancer cells, taurolidine appears to be as effective as gemcitabine, the current gold standard of cytotoxic therapy. The combination of both agents acts synergistically as compared with either monotherapy. Taurolidine has little side effects in vivo, so its use both in monotherapy and in combination with gemcitabine warrants further investigations. Studies using an orthotopic tumor model of ductal pancreatic adenocarcinoma are necessary to confirm whether this promising new drug is of relevance in a preclinical therapeutic setting.
Number of cells (x10^4/mL ± SEM) under therapy as indicated.

Gemcitabine concentration	Taurolidine concentration / µmol/L	DSL / 10^4 /mL	HPAF / 10^4 / mL
0	0	15.9 ± 4.5	33.4 ± 5.1
0	100	7.8 ± 1.8 *	15.4 ± 2.9 *
low dose	0	11.6 ± 3.8	27.1 ± 4.5
low dose	100	6.6 ± 1.4 *	12.2 ± 2.5 *
high dose	0	2.7 ± 1.8 *	16.2 ± 3.1 *
high dose	100	1.2 ± 1.7 *#	2.3 ± 1.1 *#~

Gemcitabine concentration: Low dose: 0.01 µmol/L for DSL, 1 µmol/L for HPAF. High dose: 10 µmol/L for DSL, 100 µmol/L for HPAF. * p<0.05 compared with control. # p<0.05 compared with taurolidine monotherapy. ~ p<0.05 compared with high dose gemcitabine monotherapy.