1. Resveratrol nanoparticles induce apoptosis in oral cancer stem cells by disrupting the interaction between β-catenin and GLI-1 through p53-independent activation of p21.
- Author
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Bhal S, Das B, Sinha S, Das C, Acharya SS, Maji J, and Kundu CN
- Subjects
- Humans, Animals, Mice, Cell Line, Tumor, Xenograft Model Antitumor Assays, Apoptosis drug effects, Neoplastic Stem Cells drug effects, Neoplastic Stem Cells metabolism, Neoplastic Stem Cells pathology, Resveratrol pharmacology, Zinc Finger Protein GLI1 metabolism, Zinc Finger Protein GLI1 genetics, beta Catenin metabolism, Tumor Suppressor Protein p53 metabolism, Mouth Neoplasms pathology, Mouth Neoplasms drug therapy, Mouth Neoplasms metabolism, Cyclin-Dependent Kinase Inhibitor p21 metabolism, Cyclin-Dependent Kinase Inhibitor p21 genetics, Nanoparticles
- Abstract
Cancer stem cells (CSCs) are mainly responsible for tumorigenesis, chemoresistance, and cancer recurrence. CSCs growth and progression are regulated by multiple signaling cascades including Wnt/β-catenin and Hh/GLI-1, which acts independently or via crosstalk. Targeting the crosstalk of signaling pathways would be an effective approach to control the CSC population. Both Wnt/β-catenin and Hh/GLI-1 signaling cascades are known to be regulated by p53/p21-dependent mechanism. However, it is interesting to delineate whether p21 can induce apoptosis in a p53-independent manner. Therefore, utilizing various subtypes of oral CSCs (SCC9-PEMT p53
+/+ p21+/+ , SCC9-PEMT p53-/- p21+/+ , SCC9-PEMT p53+/+ p21-/- and SCC9-PEMT p53-/- p21-/- ), we have examined the distinct roles of p53 and p21 in Resveratrol nanoparticle (Res-Nano)-mediated apoptosis. It is interesting to see that, besides the p53/p21-mediated mechanism, Res-Nano exposure also significantly induced apoptosis in oral CSCs through a p53-independent activation of p21. Additionally, Res-Nano-induced p21-activation deregulated the β-catenin-GLI-1 complex and consequently reduced the TCF/LEF and GLI-1 reporter activities. In agreement with in vitro data, similar experimental results were obtained in in vivo mice xenograft model., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)- Published
- 2024
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