Curcumin-Induced Vacuolizing Stress Reveals a Vulnerability Associated with NF1 Loss in Schwann Cells
- 1Institute of Molecular Biology and Pathology, National Research Council, 00185 Rome, Italy
Abstract
Neurofibromatosis type 1 (NF1) predisposes to peripheral nerve sheath tumors arising from Schwann-lineage cells with biallelic NF1 loss and remains in need of biologically informed strategies compatible with chronic disease management. Curcumin has attracted interest in NF1, but its effects in disease-relevant cells remain unclear. Here, we investigated curcumin responses in patient-derived NF1-deficient Schwann cells. Curcumin induced the progressive accumulation of cytoplasmic vacuoles resembling those elicited by a reference methuosis inducer, without prominent evidence of canonical apoptotic features. Vacuolization was associated with impaired long-term clonogenic recovery, indicating a durable loss of proliferative fitness. NF1-deficient Schwann cells displayed lower levels of NRF2, thioredoxin, and SOD1 than NF1-proficient cells under basal and curcumin-treated conditions, defining a distinct NF1-associated antioxidant-response context. Consistent with a functionally relevant redox-sensitive component, N-acetylcysteine pretreatment reduced curcumin-induced vacuolization to near-basal levels and substantially improved clonogenic recovery after drug washout. NF1-proficient Schwann cells showed an attenuated vacuolizing response, whereas acute NF1 silencing in hTERT RPE-1 cells enhanced curcumin-induced vacuolization in an independent cellular background. Together, these findings identify an NAC-sensitive vacuolizing response associated with loss of cellular fitness as a previously underappreciated vulnerability of NF1-deficient cells and provide a disease-relevant framework for understanding curcumin responsiveness in NF1.
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BibTeX
@article{iazzetta2026curcumininduced,
title = {{Curcumin-Induced Vacuolizing Stress Reveals a Vulnerability Associated with NF1 Loss in Schwann Cells}},
author = {Assunta Maria Iazzetta and Francesca Sardina and Cinzia Rinaldo},
journal = {Cells},
year = {2026},
month = oct,
doi = {10.3390/cells15201904},
url = {https://www.mdpi.com/2073-4409/15/20/1904},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Curcumin-Induced Vacuolizing Stress Reveals a Vulnerability Associated with NF1 Loss in Schwann Cells
AU - Assunta Maria Iazzetta
AU - Francesca Sardina
AU - Cinzia Rinaldo
PY - 2026
DA - 2026/10/20
JO - Cells
DO - 10.3390/cells15201904
UR - https://www.mdpi.com/2073-4409/15/20/1904
AB - Neurofibromatosis type 1 (NF1) predisposes to peripheral nerve sheath tumors arising from Schwann-lineage cells with biallelic NF1 loss and remains in need of biologically informed strategies compatible with chronic disease management. Curcumin has attracted interest in NF1, but its effects in disease-relevant cells remain unclear. Here, we investigated curcumin responses in patient-derived NF1-deficient Schwann cells. Curcumin induced the progressive accumulation of cytoplasmic vacuoles resembling those elicited by a reference methuosis inducer, without prominent evidence of canonical apoptotic features. Vacuolization was associated with impaired long-term clonogenic recovery, indicating a durable loss of proliferative fitness. NF1-deficient Schwann cells displayed lower levels of NRF2, thioredoxin, and SOD1 than NF1-proficient cells under basal and curcumin-treated conditions, defining a distinct NF1-associated antioxidant-response context. Consistent with a functionally relevant redox-sensitive component, N-acetylcysteine pretreatment reduced curcumin-induced vacuolization to near-basal levels and substantially improved clonogenic recovery after drug washout. NF1-proficient Schwann cells showed an attenuated vacuolizing response, whereas acute NF1 silencing in hTERT RPE-1 cells enhanced curcumin-induced vacuolization in an independent cellular background. Together, these findings identify an NAC-sensitive vacuolizing response associated with loss of cellular fitness as a previously underappreciated vulnerability of NF1-deficient cells and provide a disease-relevant framework for understanding curcumin responsiveness in NF1.
SN - 2073-4409
ER -