Abstract
BackgroundBufadienolides derived from the skin of toads are often regarded as the main active components with antitumor effects. 19-Hydroxybufalin (19-HB) is a monomer of bufadienolides; however, its effects and underlying molecular mechanisms on tumor growth remain to be ascertained. In this report, we focused on the antitumor effects of 19-HB on non-small cell lung cancer to provide a scientific basis for its further development and utilization.MethodsThe antitumor effects of 19-HB on the human NSCLC cell lines NCI-H1299 and NCI-H838 were examined in vitro. The cells were treated with different concentrations of 19-HB, and the inhibition of cell growth was measured by CCK-8 and colony formation assays. Furthermore, cell apoptosis was analyzed by flow cytometry, TUNEL staining, JC-1 staining, and western blotting. The effects on migration and invasion were evaluated by wound-healing assay, transwell assay, and western blotting. Finally, the antitumor effects of 19-HB were evaluated in vivo using a xenograft mouse model.Results19-HB-treated NSCLC cells showed inhibited cell viability and increased apoptosis. The expression levels of cleaved caspase-3, cleaved-PARP, and Bax/Bcl-2 were upregulated, while the mitochondrial membrane potential decreased. In contrast, migration, invasion, as well as the expression of MMP2, MMP7, MMP9, the epithelial–mesenchymal transition-related proteins N-cadherin and Vimentin, and the transcription factors Snail and Slug were inhibited. Furthermore, the expression levels of the key molecules in the Wnt/β-catenin signaling pathway (CyclinD1, c-Myc, and β-catenin) were decreased. In vivo, the growth of xenograft tumors in nude mice was also significantly inhibited by 19-HB, and there were no significant changes in biochemical indicators of hepatic and renal function.Conclusions19-HB inhibited the proliferation, migration, and invasion, and promoted the apoptosis of NSCLC cells via the Wnt/β-catenin pathway. In addition, 19-HB inhibited the growth of xenograft tumors in nude mice with little toxicity to the liver and kidney. Thus, 19-HB may be a potential antitumor agent for treating NSCLC.
Highlights
Bufadienolides derived from the skin of toads are often regarded as the main active components with antitumor effects. 19-Hydroxybufalin (19-HB) is a monomer of bufadienolides; its effects and underlying molecular mechanisms on tumor growth remain to be ascertained
19‐HB inhibited the activation of the Wnt/β‐catenin signaling pathway in non-small cell lung cancer (NSCLC) cells Since Wnt/β-catenin signaling pathway is important for regulating epithelial–mesenchymal transition (EMT) process, we evaluated the expression levels of β-catenin, c-Myc, and Cyclin D1 by western blotting
19‐HB inhibited the growth of NSCLC in vivo Based on the in vitro data, we further investigated the in vivo antitumor ability of 19-HB in NCI-H1299 xenograft Balb/c nude mice
Summary
Bufadienolides derived from the skin of toads are often regarded as the main active components with antitumor effects. 19-Hydroxybufalin (19-HB) is a monomer of bufadienolides; its effects and underlying molecular mechanisms on tumor growth remain to be ascertained. We focused on the antitumor effects of 19-HB on non-small cell lung cancer to provide a scientific basis for its further development and utilization. Among all lung cancer patients, approximately 85% of them suffers in non-small cell lung cancer (NSCLC) based on histological characters [2]. Immunotherapy has significantly improved the survival of patients with NSCLC or small cell lung cancer (SCLC) [3,4,5]. Majority of lung cancer patients are not benefit from immunotherapy [6]. These options only provide limited effects on the overall survival, in individuals with metastatic and chemoresistant phenotype. Searching for new molecular target and high-efficiency drugs is urgently needed [7,8,9]
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