The Antitumoral Effect of Paris Saponin II on Head and Neck Squamous Cell Carcinomas Mediated via the Nitric Oxide Metabolic Pathway.

Wenwen Qi,Baowei Wang,Xiaoming Li,Fenglei Xu,Fangyuan Zhu,Chengcheng Liu,Min Wang,Zhenxiao Teng,Yue Xi,Min Ma,Xiaozhi Hou,Ming Xia,Xiang Zhang,Runtong Xu,Qiu Meng,Hui Zhao,Xinhao Wu

doi:10.3389/fcell.2021.803981

Abstract

Paris saponin has shown great therapeutic value in cancer therapy. We used isolated Paris saponin II (PSII), an active component of Paris saponin, and demonstrated its antitumor effect on human head and neck squamous cell carcinoma cell lines. Additionally, we investigated its mechanisms of action in vivo by establishing a xenograft mouse model. The results showed that PSII had presented strong anticancer effects on both hypopharyngeal malignant tumor cell lines (FaDu) and laryngeal carcinoma cell lines (Tu212 and Tu686). In addition, we successfully isolated and cultured the head and neck squamous stem cells and the primary fibroblasts to perform metabonomics studies. The results showed that RPII remarkably decreased energy metabolism, and type III nitric oxide synthase 3 (NOS3) may be a target to block tumor growth. Furthermore, we found that PSII inhibited HNSCC proliferation and metastasis by inhibiting the nitric oxide metabolic pathway. Overall, these results demonstrated that PSII is a potent anticancer agent, and the metabonomics analysis is a valuable tool to investigate and establish the antitumor effects of traditional Chinese medicines.

Highlights

Head and neck squamous cell carcinoma is one of the most common cancers in the world (Schinke et al, 2021), and its 5-year overall survival (OS) rate is only 45% (HammermanHammerman et al, 2015; Johnson et al, 2020)
The measurement of cell proliferation by the methyl thiazolyl tetrazolium (MTT) assay, as shown in Figures 2A–C, revealed that treatment with Paris saponin II (PSII) significantly inhibited the proliferation of FaDu, Tu686, and Tu212 cells in a time- and concentration-dependent manner, especially after 48 h or at a concentration of 0.1 μg/ml PSII
Despite advances in therapeutic approaches, survival rates remain poor for patients with HNSCC (Jung et al, 2020; Kitamura et al, 2020)

Summary

Introduction

Head and neck squamous cell carcinoma is one of the most common cancers in the world (Schinke et al, 2021), and its 5-year overall survival (OS) rate is only 45% (HammermanHammerman et al, 2015; Johnson et al, 2020). A possible reason for the failure of the cancer treatment is associated with the existence of “cancer stem cells” (CSCs) in tumors, which numerous studies have shown to have a major impact on the recurrence and metastasis of tumors, as well as the resistance to radio/ chemotherapy treatment (Chen et al, 2020; Chang et al, 2021). Another possible reason is the tumor microenvironment (TME), which may have important implications for tumor therapy (Hinshaw and Shevde, 2019). Metabonomics is a promising approach to investigate the mechanisms and safety of medicine

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Conclusion