Flavonoid apigenin modified gene expression associated with inflammation and cancer and induced apoptosis in human pancreatic cancer cells through inhibition of GSK-3β/NF-κB signaling cascade

Authors

  • Jodee L. Johnson,

    1. Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, IL, USA
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  • Elvira Gonzalez de Mejia

    Corresponding author
    1. Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, IL, USA
    2. Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, IL, USA
    • Correspondence: Professor Elvira Gonzalez de Mejia, Department of Food Science and Human Nutrition, University of Illinois, 228 Edward R. Madigan Laboratory, MC-051, 1201 W Gregory Drive, Urbana-Champaign, IL 61801, USA

      E-mail: edemejia@illinois.edu

      Fax: +1-217-265-0925

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Abstract

Scope

The objective was to examine the inhibitory effects of citrus fruit bioactive compounds on BxPC-3 and PANC-1 human pancreatic cancer cells, focusing on the antiproliferative mechanism of action of the flavonoid apigenin related to the glycogen synthase kinase-3β/nuclear factor kappa B signaling pathway.

Methods and results

Flavonoids, limonoids, phenolic acids, and ascorbic acid were tested for cytotoxic effects on BxPC-3 and PANC-1 cells; apigenin was the most potent (IC50 = 23 and 12 μM for 24 and 48 h for BxPC-3 and IC50 = 71 and 41 μM for 24 and 48 h for PANC-1). Apigenin induced pancreatic cell death through inhibition of the glycogen synthase kinase-3β/nuclear factor kappa B signaling pathway. Apigenin arrested cell cycle at G2/M phase (36 and 32% at 50 μM for BxPC-3 and PANC-1, respectively) with concomitant decrease in the expression of cyclin B1. Apigenin activated the mitochondrial pathway of apoptosis (44 and 14% at 50 μM for BxPC-3 and PANC-1, respectively) and modified the expression of apoptotic proteins. Apigenin highly upregulated the expression of cytokine genes IL17F (114.2-fold), LTA (33.1-fold), IL17C (23.2-fold), IL17A (11.3-fold), and IFNB1 (8.9-fold) in BxPC-3 cells, which potentially contributed to the anticancer properties.

Conclusion

Flavonoids have a protective role in pancreatic cancer tumorigenesis.

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