Narciclasine Induces Caspase Cascade Activation and Cell Apoptosis via JNK Signaling in Oral Cancer

Abstract

Narciclasine (NCS), a plant alkaloid originally isolated from bulbs of several Narcissus species, has been demonstrated to exhibit anti-inflammatory and anticancer properties. Nevertheless, the effect of NCS on oral squamous cell carcinoma (OSCC) remains largely unexplored. In this study, we aimed to examine whether NCS inhibits OSCC progression, and further assessed the underlying mechanisms. Our findings indicate that NCS was cytotoxic to OSCC cell lines and induced both cell cycle arrest and apoptotic responses. In addition, the downregulation of many potential apoptosis inhibitors (HO-2, cIAP-1, survivin, and claspin) and activation of caspase cascades were seen in NCS-treated OSCC cells. Moreover, NCS-induced caspase activations and apoptotic responses of OSCC were affected by pretreatment with a selective JNK antagonist. This revealed the functional involvement of JNK signaling in NCS's actions on oral cancer. Taken together, our results showed that NCS stalled the cell cycle and triggered cell apoptosis in OSCC by employing a JNK-dependent activation of caspase cascades. These data offer possible avenues for the use of a naturally occurring alkaloid with therapeutic values in combating oral tumorigenesis.

Keywords: JNK; Narciclasine; apoptosis; oral squamous cancer.