Abstract

Dendrobii Herba is an herbal medicine that uses the stems of Dendrobium species (Orchidacea). It has been traditionally used to treat fever, hydrodipsomania, stomach disorders, and amyotrophia. In our previous study, a bibenzyl compound, moscatilin, which is isolated from Dendrobii Herba, showed potent cytotoxicity against a FaDu human pharyngeal squamous carcinoma cell line. Prompted by this finding, we performed additional studies in FaDu cells to investigate the mechanism of action. Moscatilin induced FaDu cell death by using 5 μM of concentration and by mediating apoptosis, whereas cell proliferation following treatment with 1 μM of moscatilin was not suppressed to the same levels as by the anti-cancer agent, cisplatin. Apoptosis-related protein expression (cleaved caspase-8, cleaved caspase-7, cytochrome c, cleaved caspase-9, cleaved caspase-3, and poly (ADP-ribose) polymerase (PARP) was increased by treating with 5 μM of moscatilin. This suggests that moscatilin-mediated apoptosis is associated with the extrinsic and intrinsic apoptotic signaling pathways. In addition, moscatilin-induced apoptosis was mediated by the c-Jun N-terminal kinase (JNK) signaling pathway. Overall, this study identified additional biological activity of moscatilin derived from natural products and suggested its potential application as a chemotherapeutic agent for the management of head and neck squamous cell carcinoma.

Highlights

  • Head and neck squamous cell carcinoma (HNSCC), arising in the oral cavity, larynx, and pharynx, is the sixth most common cancer globally, with approximately 600,000 cases diagnosed annually [1].Oncogenic stimuli for HNSCC, such as smoking, alcohol consumption, and viral infection, could serve as potential triggers [2]

  • We further investigated the mechanism of action of moscatilin using FaDu human pharyngeal squamous carcinoma cells

  • The cells were treated with varying concentrations of moscatilin and cisplatin (0.47, 0.94, 1.88, 3.75, 7.5, 15, and 30 μM) for 48 and 72 h

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Summary

Introduction

Head and neck squamous cell carcinoma (HNSCC), arising in the oral cavity, larynx, and pharynx, is the sixth most common cancer globally, with approximately 600,000 cases diagnosed annually [1]. Oncogenic stimuli for HNSCC, such as smoking, alcohol consumption, and viral infection, could serve as potential triggers [2]. Despite improvements in clinical therapeutics, such as surgery, chemotherapy, and radiotherapy, the survival rates of patients with HNSCC have not improved over the past 50 years and remain at a 50% five-year survival rate [1,2]. It is necessary to develop chemotherapeutic agents that effectively treat HNSCC. In response to this need, several studies have reported natural product-derived compounds with anti-cancer mechanisms in HNSCC [3,4,5].

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