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Curcumin inhibits tumor growth and angiogenesis in an orthotopic mouse model of human pancreatic cancer.

Bimonte S, Barbieri A, Palma G, Luciano A, Rea D, Arra C - Biomed Res Int (2013)

Bottom Line: However, gemcitabine treatment is associated with many side effects.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.

View Article: PubMed Central - PubMed

Affiliation: Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione G. Pascale", IRCCS, Via Mariano Semmola, 80131 Naples, Italy.

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.

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Molecular targets of curcumin in pancreatic cancer cells.
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Related In: Results  -  Collection


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fig4: Molecular targets of curcumin in pancreatic cancer cells.

Mentions: Since it has been demonstrated that curcumin potentiates the antitumor activity of gemcitabine in pancreatic cells by downregulating NF-κB-regulated gene products [17], we performed DNA binding to detect NF-κB expression in orthotopic tumor tissue samples from control and treated mice. Our results showed the inhibition of NF-κB activation by curcumin (Figure 3(a), lane 2). Since it has been demonstrated that NF-κB regulates the expression of several markers involved in proliferation (COX-2, cyclin D1), in invasion (MMP-9), and in angiogenesis (VEGF), we performed an immunohistochemical analysis and Western blotting on orthotopic tumor tissue samples from control and treated mice. Immunoistochemical analysis indicates that, in tumors of curcumin-treated group, there are significant reductions in the expression of COX-2 and VEGF, compared with the control group (Figure 3(b)). Western blotting analysis revealed that curcumin, significantly decreased the expression of all of these molecules compared with the control treatment in pancreatic tumor tissues (Figure 3(c)). We finally performed a western blot analysis with IKKα and IKKβ in order to understand how curcumin inhibits NF-κB activation in MIA PaCa-2 cells. Our data indicated that there is a reduced expression of IKKα and IKKβ in tumor of mice treated with curcumin with respect to controls, indicating that curcumin inhibits NF-κB activation through suppression of IKK (Figure 3(c)). Figure 4 shows a schematic diagram which contextualizes the various signalling cascades affected by curcumin in pancreatic cancer cells. Altogether, these data indicate that curcumin inhibits NF-κB activation and down-regulates NF-κB-regulated gene products in orthotopic pancreatic tumors.


Curcumin inhibits tumor growth and angiogenesis in an orthotopic mouse model of human pancreatic cancer.

Bimonte S, Barbieri A, Palma G, Luciano A, Rea D, Arra C - Biomed Res Int (2013)

Molecular targets of curcumin in pancreatic cancer cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3842048&req=5

fig4: Molecular targets of curcumin in pancreatic cancer cells.
Mentions: Since it has been demonstrated that curcumin potentiates the antitumor activity of gemcitabine in pancreatic cells by downregulating NF-κB-regulated gene products [17], we performed DNA binding to detect NF-κB expression in orthotopic tumor tissue samples from control and treated mice. Our results showed the inhibition of NF-κB activation by curcumin (Figure 3(a), lane 2). Since it has been demonstrated that NF-κB regulates the expression of several markers involved in proliferation (COX-2, cyclin D1), in invasion (MMP-9), and in angiogenesis (VEGF), we performed an immunohistochemical analysis and Western blotting on orthotopic tumor tissue samples from control and treated mice. Immunoistochemical analysis indicates that, in tumors of curcumin-treated group, there are significant reductions in the expression of COX-2 and VEGF, compared with the control group (Figure 3(b)). Western blotting analysis revealed that curcumin, significantly decreased the expression of all of these molecules compared with the control treatment in pancreatic tumor tissues (Figure 3(c)). We finally performed a western blot analysis with IKKα and IKKβ in order to understand how curcumin inhibits NF-κB activation in MIA PaCa-2 cells. Our data indicated that there is a reduced expression of IKKα and IKKβ in tumor of mice treated with curcumin with respect to controls, indicating that curcumin inhibits NF-κB activation through suppression of IKK (Figure 3(c)). Figure 4 shows a schematic diagram which contextualizes the various signalling cascades affected by curcumin in pancreatic cancer cells. Altogether, these data indicate that curcumin inhibits NF-κB activation and down-regulates NF-κB-regulated gene products in orthotopic pancreatic tumors.

Bottom Line: However, gemcitabine treatment is associated with many side effects.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.

View Article: PubMed Central - PubMed

Affiliation: Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione G. Pascale", IRCCS, Via Mariano Semmola, 80131 Naples, Italy.

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.

Show MeSH
Related in: MedlinePlus