Curcumin Inhibits Tumor Growth and Angiogenesis in an Orthotopic Mouse Model of Human Pancreatic Cancer

Sabrina Bimonte,Giuseppe Palma,Antonio Barbieri,Antonio Luciano,Claudio Arra,Domenica Rea

doi:10.1155/2013/810423

Abstract

Pancreatic cancer is a malignant neoplasm originating from transformed cells arising in tissues forming the pancreas. The best chemotherapeutic agent used to treat pancreatic cancer is the gemcitabine. However, gemcitabine treatment is associated with many side effects. Thus novel strategies involving less toxic agents for treatment of pancreatic cancer are necessary. Curcumin is one such agent that inhibits the proliferation and angiogenesis of a wide variety of tumor cells, through the modulation of many cell signalling pathways. In this study, we investigated whether curcumin plays antitumor effects in MIA PaCa-2 cells. In vitro studies showed that curcumin inhibits the proliferation and enhances apoptosis of MIA PaCa-2 cells. To test whether the antitumor activity of curcumin is also observed in vivo, we generated an orthotopic mouse model of pancreatic cancer by injection of MIA PaCa-2 cells in nude mice. We placed mice on diet containing curcumin at 0.6% for 6 weeks. In these treated mice tumors were smaller with respect to controls and showed a downregulation of the transcription nuclear factor NF-κB and NF-κB-regulated gene products. Overall, our data indicate that curcumin has a great potential in treatment of human pancreatic cancer through the modulation of NF-κB pathway.

Highlights

Pancreatic cancer is a malignant neoplasm originating from transformed cells arising in tissues forming the pancreas, and it is the fourth most common cause of cancerrelated deaths in the United States and the eighth worldwide [1]
Our results showed that the percentage of apoptosis of MIA PaCa-2 cells treated with curcumin was higher with respect to controls and to MPanc-96 and Panc-1 cells (Figure 1(h))
It has been demonstrated that curcumin modulates the activation of the transcription factor nuclear factor-κB (NF-κB) for this reason, we performed a nuclear NF-κB DNA binding assay on MIA PaCA-2 cells treated with curcumin and controls, and we demonstrated that curcumin downregulated NFκB activation in MIA PaCa-2 cells (Figure 1(i))

Summary

Introduction

Pancreatic cancer is a malignant neoplasm originating from transformed cells arising in tissues forming the pancreas, and it is the fourth most common cause of cancerrelated deaths in the United States and the eighth worldwide [1]. This pathology leads to an aggressive local invasion and early metastases, and is poorly responsive to treatment with chemotherapy [2]. A component of the spice turmeric (Curcuma longa), is one such agent and is not toxic to humans [4]. It has been demonstrated that NF-κB plays

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