Castalin Induces ROS Production, Leading to DNA Damage and Increasing the Activity of CHK1 Inhibitor in Cancer Cell Lines
(1) Background: The use of cancer therapy is one of the most challenging arguments in cancer research and is in constant development. One of the principal problems connected with tumor therapy arises from the potential side effects connected with the classical chemotherapeutic treatment but also with molecular target therapy. The identification of novel molecules useful for the reduction of potential side effects but also as a new therapeutic opportunity is one of the hottest topics. (2) Methods: We identified castalin from chestnut shells by using NRM and LC-MS/MS. We treated different cancer cell lines with castalin alone or in combination with a CHK1 inhibitor. Finally, we performed an RNA-seq analysis of HeLa cells treated with castalin. (3) Results: We demonstrated the ability of castalin to induce DNA damage, probably by increasing ROS production. Consistently, antioxidant treatment, with ascorbic acid, reduced the DNA damage induced by castalin. Finally, we demonstrated the potential synergistic effect of castalin with SRA737, a CHK1 inhibitor currently used in clinical trials. (4) Conclusions: We demonstrated the ability of castalin to induce DNA damage favoring NHEJ repair. Moreover, the use of castalin in combination with SRA737 increased the efficacy of the CHK1 inhibitor, reducing its possible side effects.
Authors
- Raffaele Cucciniello (ORCID: https://orcid.org/0000-0002-3291-7273)
- Enrico Bucci (ORCID: https://orcid.org/0009-0006-2335-9819)
- Annamaria Salvati (ORCID: https://orcid.org/0000-0002-9601-2975)
- Luigi Alfano (ORCID: https://orcid.org/0000-0002-4516-9956)
- Domenico Memoli (ORCID: https://orcid.org/0000-0001-5290-2709)
- Antonio Giordano (ORCID: https://orcid.org/0000-0002-5959-016X)
- Francesco Errichiello (ORCID: https://orcid.org/0000-0003-4317-4628)
- Michelino De Laurentiis (ORCID: https://orcid.org/0000-0001-9009-1572)
- Carmelina Antonella Iannuzzi (ORCID: https://orcid.org/0000-0002-4445-9687)
- Maria Concetta Cuomo (ORCID: https://orcid.org/0009-0000-1847-0279)
- Giuliana Napolitano (ORCID: https://orcid.org/0000-0002-1637-6016)
- Giovanni Nassa (ORCID: https://orcid.org/0000-0001-7453-1240)
- Luigi Frusciante
- Canio Martinelli (ORCID: https://orcid.org/0000-0002-0587-8467)
- Maria Carmen Ragosta (ORCID: https://orcid.org/0009-0002-9311-632X)
- Giulio Mazzarotti (ORCID: https://orcid.org/0009-0002-9700-2290)
- Margherita D’Angelo
- Andrea Russo (ORCID: https://orcid.org/0009-0007-7236-4830)
- Annamaria Medugno (ORCID: https://orcid.org/0009-0001-6314-4488)
Institutions
- University of Siena (IT)
- University of Salerno (IT)
- Institute for Scientific Interchange (IT)
- University of Campania "Luigi Vanvitelli" (IT)
- Azienda Ospedaliera Universitaria Università degli Studi della Campania Luigi Vanvitelli (IT)
- Ospedali Riuniti San Giovanni di Dio e Ruggi d'Aragona (IT)
- Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale" (IT)
- Scuola Superiore Meridionale (IT)
- Temple University (US)
Publication Details
- Journal
- Antioxidants
- Published
- 2025-09-08
- DOI
- https://doi.org/10.3390/antiox14091096
- Primary Topic
- Plant biochemistry and biosynthesis
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- European Commission
- Ministero della Salute