Bis-type Triaziquone Induces PARP1-mediated Cell Death in Human NPC/HK1 Nasopharyngeal Carcinoma Cells

Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor with a high prevalence in Southeast Asia, Southern China, Singapore, and Taiwan. Despite advances in chemo-radiotherapy, approximately 30% of patients with NPC still have a poor prognosis due to distant metastasis, underscoring the urgent need for novel therapeutic agents. This study aimed to investigate the anticancer mechanism of a novel compound, bis-type triaziquone (BTZQ), in NPC cells.

NPC/HK1 cells and immortalized nasopharyngeal epithelial NP69 cells were used. Cell viability, protein expression, cytokeratin 18 fragment release, and mitochondrial membrane potential (MMP) changes were assessed using the MTT assay, immunoblotting, ELISA, and JC-1 staining, respectively.

BTZQ reduced NPC/HK1 cell viability (IC₅₀=0.38 μM) more effectively than that of NP69 cells (IC₅₀=1.53 μM), indicating selective cytotoxicity. BTZQ did not significantly increase apoptotic markers, including cleaved caspase-3, Bax, cleaved PARP1, and cytokeratin 18 fragment. Instead, BTZQ markedly elevated poly(ADP-ribose) levels, disrupted MMP, nuclear PARP1 levels, and promoted nuclear translocation of apoptosis-inducing factor, consistent with the induction of PARP1-mediated cell death (also referred to as parthanatos). Inhibition of PARP1 activity by 3-ABA or DPQ reversed BTZQ-induced loss of cell viability, confirming that PARP1 is involved in BTZQ-mediated cytotoxicity.

BTZQ selectively inhibits NPC cell viability by inducing PARP1-mediated cell death rather than apoptosis. These findings identify BTZQ as a promising candidate for NPC therapy and suggest that targeting PARP1-mediated cell death may represent a novel therapeutic strategy for this malignancy.