Narciclasine triggers apoptosis in osteosarcoma cells via JNK-mediated extrinsic and intrinsic pathways

TL;DR

Narciclasine causes osteosarcoma cells to die through JNK-related pathways, offering a potential treatment for this aggressive bone cancer.

Contribution

This study reveals that JNK signaling is crucial for narciclasine-induced apoptosis in osteosarcoma cells.

Findings

Narciclasine induces apoptosis and sub-G1 cell cycle arrest in osteosarcoma cells.

JNK inhibition reduces narciclasine-induced caspase activation and apoptosis.

JNK mediates both extrinsic and intrinsic apoptotic pathways in this context.

Abstract

Osteosarcoma, the most prevalent bone cancer in teenagers, constitutes 3-5% of pediatric cancers and carries a poor prognosis due to its high metastatic potential. Although narciclasine induces apoptosis in various cancers, its effects on human osteosarcoma cells remain unclear. This study investigated the apoptotic impact of narciclasine on U2OS and HOS osteosarcoma cells. It was found that narciclasine induces dose-dependent apoptosis and sub-G1 phase cell cycle arrest. Human apoptosis array and Western blot analyses showed reduced inhibitors of apoptosis 1 (cIAP-1) and survivin expression while increasing cleaved caspases (8, 9, and 3) and PARP. Narciclasine activated extracellular signal-regulated protein kinases (ERK)1/2, c-Jun N-terminal kinases (JNK)1/2, and p38 phosphorylation. However, the JNK inhibitor (JNK-IN-8) suppressed the narciclasine-induced increase in cleaved caspase expression and apoptosis, whereas ERK and p38 inhibitors had no effect. These findings highlight the central role of JNK signaling in mediating extrinsic and intrinsic apoptotic pathways in osteosarcoma cells treated with narciclasine.

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