Abstract
AimsThis study aimed at investigating the role of Brusatol (BR) on human laryngeal squamous carcinoma cell (Hep-2) to study its underlying mechanism through in vitro and in vivo approaches. Materials and methodIn the present research, we employed various cell-based assays, such as cell proliferation, apoptosis, cell cycle assessment, migration and invasion assays were used to examine the anti-tumor effect of BR on Hep-2 cells. Immunohistochemistry (IHC), qRT-PCR and Western blotting were performed to study the underlying molecular mechanisms. To validate our in vitro findings we used a subcutaneous tumor-bearing model of Balb/c mice with Hep-2 cells of laryngeal carcinoma (LC) to study the inhibitory effect of BR on Hep-2 cells in vivo. Key findingsThe results indicated that BR markedly inhibited the viability, migration and invasion capacity of Hep-2 cells, with no significant toxic effect on normal Human bronchial epithelial cell line (BEAS-2B). Also, BR induced cellular apoptosis by blocking the cells in S phase to suppress cell proliferation. Immunohistochemistry results revealed that BR inhibited the protein expression levels of epithelial-mesenchymal transition (EMT)-related markers. Mechanistically, western blotting results exhibited that BR could suppress the protein expression of both JAK2/STAT3 and their phosphorylation levels. Our in vivo experiments further validated the anti-tumor effect of BR on Hep-2 cells in vitro, where BR suppressed the growth of xenograft laryngeal tumor without apparent toxicity. SignificanceThe present study highlights the anti-LC effect of BR by possibly abrogating JAK2/STAT3 signaling mediated EMT process. BR may be a promising therapeutic candidate for the treatment of LC.
Highlights
Laryngeal cancer (LC) is the second most widespread malignancy of the upper aerodigestive tract squamous cell carcinoma, which is characterized by hoarseness, sore throat and persistent cough [1, 2]
Conclusions: the present study revealed that the anti-LC effect of BR might be closely relevant to abrogation of janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling mediated epithelialmesenchymal transition (EMT) process
About 95% of laryngeal carcinoma are diagnosed as laryngeal squamous cell carcinoma (LSCC) [3]
Summary
Laryngeal cancer (LC) is the second most widespread malignancy of the upper aerodigestive tract squamous cell carcinoma, which is characterized by hoarseness, sore throat and persistent cough [1, 2]. Surgery and chemotherapy are the most common therapies for the treatment of LC [5]. Anti-tumor agent from natural plants is one of alternative treatment options and has been increasingly recognized worldwide. Brusatol (BR) is a principal bioactive quassinoid derived from the Chinese medicinal plant Brucea javanica, which has recently been reported to exert notable cytotoxic effects against numerous cancer cell lines. We have investigated the effects of BR on human laryngeal squamous carcinoma cell (Hep-2) and explored its underlying mechanism both in vitro and in vivo experiments
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