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Synergistic effects of multiple natural products in pancreatic cancer cells
Zhiwei Wang1, Sita Desmoulin, Sanjeev Banerjee
1Department of Pathology, Karmanos Cancer Institute, Wayne State University, Detroit, Michigan, United States.
Abstract:
Pancreatic cancer (PC) remains the fourth most common cause of cancer related death in the United States. Therefore, novel strategies for the prevention and treatment are urgently needed. Numerous dietary and pharmacological agents have been proposed as alternative strategies for the prevention and/or treatment of PC. Isoflavone is a prominent flavonoid found in soy products and has been proposed to be responsible for lowering the incidence of PC in Asians. Similarly, curcumin, an active ingredient of turmeric, that inhibits growth of malignant neoplasms, has a promising role in the prevention and/or treatment of PC. Here we examined whether isoflavone together with curcumin could elicit a greater inhibition of growth of PC cells than either agent alone, and also sought to determine the molecular mechanism of action. We found that the inhibition of cell growth and induction of apoptosis was significantly greater in the combination group than that could be achieved by either agent alone. These changes were associated with decreased Notch-1 expression and DNA binding activity of NF-kappaB and its target genes such as Cyclin D1, Bcl-2, and Bcl-xL. Moreover, we found that the combination of four natural agents at lower concentration was much more effective. Collectively, our results suggest that diet containing multiple natural products should be preferable over single agents for the prevention and/or treatment of PC. The superior effects of the combinatorial treatment could partly be attributed to the inhibition of constitutive activation of Notch-1 and NF-kappaB signaling pathways.
Insights
Combining isoflavone and curcumin significantly inhibits pancreatic cancer (PC) cell growth and induces apoptosis. This combination therapy, potentially involving multiple natural products, offers a promising strategy for PC prevention and treatment.
Area of Science:
- Oncology
- Molecular Biology
- Nutritional Science
Background:
- Pancreatic cancer (PC) is a leading cause of cancer-related death in the US, necessitating novel prevention and treatment strategies.
- Dietary agents like isoflavones (from soy) and curcumin (from turmeric) show potential in PC prevention and treatment.
- Investigating combined effects of these natural compounds is crucial for developing effective therapies.
Purpose of the Study:
- To evaluate the synergistic effect of isoflavone and curcumin on pancreatic cancer cell growth inhibition and apoptosis.
- To elucidate the molecular mechanisms underlying the combined action of isoflavone and curcumin.
- To assess the efficacy of combining multiple natural agents for pancreatic cancer treatment.
Main Methods:
- In vitro studies on pancreatic cancer cells treated with isoflavone, curcumin, or their combination.
- Analysis of cell growth inhibition and apoptosis induction.
- Assessment of molecular targets including Notch-1 expression and NF-kappaB signaling pathway activity.
Main Results:
- The combination of isoflavone and curcumin demonstrated significantly greater inhibition of PC cell growth and induction of apoptosis compared to individual agents.
- Combined treatment led to decreased Notch-1 expression and reduced DNA binding activity of NF-kappaB and its target genes (Cyclin D1, Bcl-2, Bcl-xL).
- A combination of four natural agents at lower concentrations proved highly effective.
Conclusions:
- Combination therapy with isoflavone and curcumin exhibits superior efficacy in inhibiting pancreatic cancer cell growth and inducing apoptosis.
- The synergistic effect is partly mediated by the inhibition of Notch-1 and NF-kappaB signaling pathways.
- Dietary strategies incorporating multiple natural products may be more beneficial than single agents for pancreatic cancer prevention and treatment.
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