Celastrol and Its Derivatives in Breast, Ovarian, and Cervical Cancer: Molecular Targets, Signalling Networks, and Nanocarrier-Based Delivery
10 affiliations
- 1Department of Economic and Medical Informatics, University of Lodz, 90-214 Lodz, Poland
- 2Students Research Group, Department of Medical Biology, Medical University of Lodz, 90-151 Lodz, Poland
- 3Department of Molecular Biotechnology and Genetics, Faculty of Biology and Environmental Protection, University of Lodz, Banacha 12/16, 90-237 Lodz, Poland
- 4Students Research Club NANO, Department of Chemistry, Lodz University of Technology, Stefanowskiego 16, 90-537 Lodz, Poland
- 5Department of Surgical Oncology, Medical University of Lodz, 251 Pomorska St., 93-513 Lodz, Poland
- 6Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Jagiellońska 13-15, 85-067 Bydgoszcz, Poland
- 7Eurecat, Centre Tecnològic de Catalunya, C/Marcel·lí Domingo 2, 43007 Tarragona, Spain
- 8Littoral Environnement et Sociétés UMRi CNRS 7266 LIENSs, La Rochelle Université, 17042 La Rochelle, France
- 9Chemistry Interdisciplinary Project (ChIP) Research Center, School of Pharmacy, University of Camerino, Via Madonna delle Carceri, 62032 Camerino, Italy
- 10Department of Medical Biology, Medical University of Lodz, Muszyńskiego 1, 90-151 Lodz, Poland
Abstract
Celastrol, a quinone methide pentacyclic triterpenoid obtained mainly from the roots of Tripterygium wilfordii Hook. f., forms covalent, often reversible, adducts with cysteine thiols in regulatory proteins, which underlies its multi-targeted action. This review summarises the preclinical evidence on celastrol and its derivatives in breast, ovarian, and cervical cancer and the nanocarriers designed to overcome its pharmacological limitations. Chemoproteomics has defined covalent targets at three distinguishable levels of evidence: residue-mapped and confirmed by mutagenesis or by genetic validation for IKKβ, PRDX1, PKM2, HMGB1, and COMMD3; binding measured without mapping of the residue for the Hsp90–Cdc37 complex, the proteasome, further peroxiredoxins, and mitochondrial isocitrate dehydrogenases; and inferred from functional or degradation readouts for the remainder. Almost all of this work was performed outside the three tumour types, so the target catalogue applies to them by extrapolation. Across in vitro and in vivo models it induces cell-cycle arrest, apoptosis, and oxidative and mitochondrial stress, modulates NF-κB, PI3K/Akt/mTOR, JAK/STAT3, MAPK, Wnt/β-catenin, and Hippo signalling, and limits migration, invasion, and angiogenesis. It also engages paraptosis, endoplasmic reticulum stress, pyroptosis, ferroptosis, cuproptosis, and immunogenic cell death, and remodels the tumour immune microenvironment. Modification at the C-20 carboxyl group and the A/B ring system, including proteolysis-targeting chimeras, has improved potency and selectivity. Because solubility, oral bioavailability, and the therapeutic window remain limiting, liposomal, micellar, carrier-free, and biomimetic nanocarriers have been developed to improve tumour selectivity and safety. Translation will depend on optimised derivatives, advanced delivery, sustainable production, rigorous pharmacokinetic and toxicological evaluation, and the pharmacoeconomic considerations examined here.
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BibTeX
@article{mereczsadowska2026celastrol,
title = {{Celastrol and Its Derivatives in Breast, Ovarian, and Cervical Cancer: Molecular Targets, Signalling Networks, and Nanocarrier-Based Delivery}},
author = {Anna Merecz-Sadowska and Maciej Kowalski and Tomasz Kowalczyk and Maksymilian Trzciński and Martyna Muskała and Janusz Piekarski and Bartosz Tylkowski and Laurent Picot and Filippo Maggi and Przemysław Sitarek},
journal = {Molecules},
year = {2026},
month = oct,
doi = {10.3390/molecules31203641},
url = {https://hal.science/hal-05804817v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Celastrol and Its Derivatives in Breast, Ovarian, and Cervical Cancer: Molecular Targets, Signalling Networks, and Nanocarrier-Based Delivery
AU - Anna Merecz-Sadowska
AU - Maciej Kowalski
AU - Tomasz Kowalczyk
AU - Maksymilian Trzciński
AU - Martyna Muskała
AU - Janusz Piekarski
AU - Bartosz Tylkowski
AU - Laurent Picot
AU - Filippo Maggi
AU - Przemysław Sitarek
PY - 2026
DA - 2026/10/01
JO - Molecules
DO - 10.3390/molecules31203641
UR - https://hal.science/hal-05804817v1
AB - Celastrol, a quinone methide pentacyclic triterpenoid obtained mainly from the roots of Tripterygium wilfordii Hook. f., forms covalent, often reversible, adducts with cysteine thiols in regulatory proteins, which underlies its multi-targeted action. This review summarises the preclinical evidence on celastrol and its derivatives in breast, ovarian, and cervical cancer and the nanocarriers designed to overcome its pharmacological limitations. Chemoproteomics has defined covalent targets at three distinguishable levels of evidence: residue-mapped and confirmed by mutagenesis or by genetic validation for IKKβ, PRDX1, PKM2, HMGB1, and COMMD3; binding measured without mapping of the residue for the Hsp90–Cdc37 complex, the proteasome, further peroxiredoxins, and mitochondrial isocitrate dehydrogenases; and inferred from functional or degradation readouts for the remainder. Almost all of this work was performed outside the three tumour types, so the target catalogue applies to them by extrapolation. Across in vitro and in vivo models it induces cell-cycle arrest, apoptosis, and oxidative and mitochondrial stress, modulates NF-κB, PI3K/Akt/mTOR, JAK/STAT3, MAPK, Wnt/β-catenin, and Hippo signalling, and limits migration, invasion, and angiogenesis. It also engages paraptosis, endoplasmic reticulum stress, pyroptosis, ferroptosis, cuproptosis, and immunogenic cell death, and remodels the tumour immune microenvironment. Modification at the C-20 carboxyl group and the A/B ring system, including proteolysis-targeting chimeras, has improved potency and selectivity. Because solubility, oral bioavailability, and the therapeutic window remain limiting, liposomal, micellar, carrier-free, and biomimetic nanocarriers have been developed to improve tumour selectivity and safety. Translation will depend on optimised derivatives, advanced delivery, sustainable production, rigorous pharmacokinetic and toxicological evaluation, and the pharmacoeconomic considerations examined here.
SN - 1420-3049
ER -