AI Article Synopsis
- The study explores the effects of garcinol, a dietary phytochemical, on pancreatic cancer (PaCa) cells and its ability to enhance the efficacy of gemcitabine, a common chemotherapy drug.
- Garcinol was found to inhibit cell growth and promote cell death in PaCa cells, impacting several cancer regulatory proteins and altering the expression of specific microRNAs associated with cancer pathways.
- These findings suggest that combining garcinol with gemcitabine could help overcome drug resistance in PaCa treatment, highlighting the potential for this combination therapy in clinical applications.
Article Abstract
Background: Alterations in microRNA (miRNA/miR) genes are of biological importance in the pathophysiology of cancers, including pancreatic cancer (PaCa). Although growing evidence supports the role of miRNA in cancer, their response to dietary phytochemicals is less known. Previously, we showed that garcinol induces PaCa cell growth arrest and apoptosis in vitro. The present study, discusses chemo-sensitization by garcinol in synergism with first-line PaCa drug, gemcitabine. The miRNA expression profile of gemcitabine-resistant Panc-1 cells treated with garcinol and/or gemcitabine was also evaluated.
Methods And Results: Garcinol synergizes with gemcitabine to inhibit cell proliferation and induce apoptosis in PaCa cells with significant modulation of key cancer regulators including PARP, VEGF, MMPs, ILs, caspases, and NF-κB. In addition, biostatistical analyses, quantitative reverse transcription PCR data, and in silico modeling using TargetScan5, PicTar, and DNA intelligent analysis, microT-V.B4 database showed that these two agents modulated a number of microRNAs (miR-21, miR-196a, miR-495, miR-605, miR-638, and miR-453) linked to various canonical oncogenic signaling pathways.
Conclusion: We identified garcinol-specific miRNA biomarkers that sensitize PaCa cells to gemcitabine treatment, thus attenuating the drug-resistance phenotype. These results prompt further interest in garcinol and gemcitabine combination strategy as a drug modality to improve treatment outcome in patients diagnosed with PaCa.
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| http://dx.doi.org/10.1002/mnfr.201200297 | DOI Listing |
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