Abstract
Pancreatic cancer is one of the most aggressive malignancies and is characterized by a low 5-year survival rate, a broad genetic diversity and a high resistance to conventional therapies. As a result, novel therapeutic agents to improve the current situation are needed urgently. Curcumin, a polyphenolic colorant derived from Curcuma longa root, showed pleiotropic influences on cellular pathways in vitro and amongst others anti-cancer properties including sensitization of tumor cells to chemo- and radiation-therapy. In this study, we evaluated the impact of Curcumin on the radiosensitivity of the established human pancreatic cancer cell lines Panc-1 and MiaPaCa-2 in vitro. In contrast to MiaPaCa-2 cells, we found a significant radiosensitization by Curcumin in the more radioresistant Panc-1 cells, possibly caused by cell cycle arrest in the most radiation-sensitive G2/M-phase at the time of irradiation. Furthermore, a significant enhancement of radiation-induced apoptosis, DNA-double-strand breaks and G2/M-arrest after curcumin treatment was observed in both cell lines. These in vitro findings suggest that especially patients with more radioresistant tumors could benefit from a radiation-concomitant, phytotherapeutic therapy with Curcumin.
Highlights
Pancreatic cancer is one of the most aggressive malignancies and is characterized by a low 5-year survival rate, a broad genetic diversity and a high resistance to conventional therapies
The influence of curcumin on multiple cellular pathways like NFkB, PI3-kinase- or p53-activity leading to inhibition of proliferation and induction of apoptosis was shown in preclinical models of different tumor entities, including pancreatic cancer[13,14,15]
To investigate the radiosensitivity of pancreatic cancer cell lines Panc-1 and MiaPaCa-2, cells were seeded for Colony forming assay (CFA) and irradiated with doses of 0, 2, 4, 6 and 8 Gy
Summary
Pancreatic cancer is one of the most aggressive malignancies and is characterized by a low 5-year survival rate, a broad genetic diversity and a high resistance to conventional therapies. A polyphenolic colorant derived from Curcuma longa root, showed pleiotropic influences on cellular pathways in vitro and amongst others anti-cancer properties including sensitization of tumor cells to chemo- and radiation-therapy. We evaluated the impact of Curcumin on the radiosensitivity of the established human pancreatic cancer cell lines Panc-1 and MiaPaCa-2 in vitro. A significant enhancement of radiation-induced apoptosis, DNA-double-strand breaks and G2/M-arrest after curcumin treatment was observed in both cell lines These in vitro findings suggest that especially patients with more radioresistant tumors could benefit from a radiationconcomitant, phytotherapeutic therapy with Curcumin. The effect of Curcumin on radiosensitivity of the established human pancreatic cancer cell lines Panc-1 and MiaPaCa-2, as well as the effects of a combined treatment on cell cycle distribution, apoptosis and yH2AX-phosphorylation were investigated in vitro
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