Chloroethylnitrosourea analogue HJ03 overcomes temozolomide resistance of glioblastoma in mice through induction of ferroptosis and apoptosis - PubMed
4 hours ago
- #chemoresistance
- #glioblastoma
- #ferroptosis
- HJ03, a chloroethylnitrosourea analogue, overcomes temozolomide (TMZ) resistance in glioblastoma (GBM) by inducing ferroptosis and apoptosis.
- HJ03 is more potent than TMZ in inhibiting GBM cell lines, including those with MGMT overexpression or MMR dysfunction.
- HJ03 induces DNA damage and ferroptosis, leading to cell cycle arrest (G2/M phase) and apoptosis in GBM cells.
- HJ03 upregulates p53 and ATF3 while downregulating SLC7A11, causing ROS and Fe2+ accumulation and increased MDA levels.
- HJ03 crosses the blood-brain barrier more efficiently than TMZ and shows lower bone marrow toxicity.
- In mice with orthotopic GBM tumors, HJ03 significantly prolonged lifespan and synergized with radiotherapy and anti-PD-1 therapy.
- HJ03 is a promising candidate for treating TMZ-resistant GBM.