Dihydroisotanshinone I as a Treatment Option for Head and Neck Squamous Cell Carcinomas.

Cheng-Ming Hsu,Ching-Yuan Wu,Geng-He Chang,Yao-Hsu Yang,Yao-Te Tsai,Ming-Yu Yang,Shun-Fu Chang,Ming-Shao Tsai

doi:10.3390/ijms22168881

Abstract

Head and neck squamous cell carcinomas (HNSCCs) are the most common cancers of the head and neck, and their prevalence is rapidly increasing. HNSCCs present a clinical challenge because of their high recurrence rate, therapeutic resistance to radiation and chemotherapy drugs, and adverse effects. Hence, traditional Chinese herbal treatment may be advantageous to therapeutic strategies for HNSCCs. Danshen (Salvia miltiorrhiza), a well-known Chinese herb, has been extensively applied in treatments for various diseases, including cancer, because of its high degree of safety and low rate of adverse effects despite its unclear mechanism. Thus, we aimed to explore the possible anticancer effects and mechanisms of dihydroisotanshinone I (DT), a compound in danshen (extract from danshen), on HNSCCs. Three HNSCCs cell lines were used for in vitro studies, and a Detroit 562 xenograft mouse model was chosen for in vivo studies. Our in vitro results showed that DT could initiate apoptosis, resulting in cell death, and the p38 signaling partially regulated DT-initiated cell apoptosis in the Detroit 562 model. In the xenograft mouse model, DT reduced tumor size with no obvious adverse effect of hepatotoxicity. The present study suggests that DT is a promising novel candidate for anti-HNSCCs therapy.

Highlights

Head and neck squamous cell carcinomas (HNSCCs) are the most common cancers of the head and neck and mainly occur in the epithelial mucosa of the oral cavity, pharynx, and larynx [1,2]
To investigate whether dihydroisotanshinone I (DT) inhibits the survival of HNSCCs cells, three HNSCCs cell lines, namely, Detroit 562, SCC-4, and SCC-25, were treated with DT (1, 3, 5, and 10 μM) for 24 and 48 h, and survival rates were assessed by mitochondrial conversion of the 3-(4,5-dimethylthiazol-2-yl)-2,5diphenyltetrazolium bromide (MTT) assay
We examined the ability of DT, a key tanshinone in danshen, to inhibit the survival and growth of HNSCCs in Detroit 562 and SCC-4/SCC-25 cells as well as in a xenograft mouse model

Summary

Introduction

Head and neck squamous cell carcinomas (HNSCCs) are the most common cancers of the head and neck and mainly occur in the epithelial mucosa of the oral cavity, pharynx, and larynx [1,2]. The prevalence of HNSCCs is increasing rapidly, and the incidence of HNSCCs is anticipated to rise by 30% by 2030. HNSCCs are the top ten cancers worldwide according to several epidemiological studies [3,4,5]; HNSCCs are the fifth leading cause of cancer death in Taiwan [6]. The therapeutic strategy for HNSCCs comprise surgical resection with chemotherapy or adjuvant radiation [7,8,9,10]. It is not uncommon that tumor recurrence and adverse response occur especially in patients with recurrent HNSCCs [2]

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