Influence of Sodium New Houttuyfonate as a New EGFR-TK Inhibitor on the Apoptosis and Autophagy of MCF-7 Cells and Its Toxicity to Caenorhabditis elegans

Abstract

Sodium new houttuyfonate (SNH) is volatile oil extracted from Houttuynia cordata Thunb. Its molecular formula is C14H27O5SNa, and molecular weight is 330.41. It is a new anti-inflammatory drug that has been used clinically over recent years. In this work, the binding interaction simulation study on SNH and epidermal growth factor receptor-tyrosine kinase (EGFR-TK) was conducted. SNH demonstrated a good binding ability to EGFR-TK and formed hydrogen-bonds with Cys773, Asp776, and Tyr777. This indicated that SNH might play an antitumor role as a potential inhibitor of EGFR-TK. In vitro, after treatment with various doses of SNH for 48 h, the viability of MCF-7 cells was 100.0, 98.23, 83.45, 76.24, 68.53, and 32.24, respectively, accompanied by a concentration increase in SNH. Moreover, cell viability of 250 μg/mL group decreased by more than 30%. Meanwhile, SNH significantly decreased cell cloning ability, and the quantities of clones were 456, 283, 137, and 152 in different groups (0 μg/mL, 100 μg/mL, 200 μg/mL, 250 μg/mL). In addition, SNH of different concentrations promoted the apoptosis of MCF-7 cells, which showed certain morphological characteristics of apoptotic cells including loss of cell adhesiveness, nuclear shrinkage, and appearance of apoptotic bodies. Furthermore, SNH effectively attenuated the migration of MCF-7 cells by decreasing the expressions of NF-kBp65 and vascular endothelial growth factor (VEGF). The increased number of apoptotic cells was also observed through hoechst33258 staining and Annexin V-PI staining, which corroborated with the decreased ratio of Bax and Bcl-2. Moreover, SNH induced the appearance of LC3 positive autophagosomes in MCF-7 cells. In vivo, SNH showed obvious antinematode activity, and LC50 was 40.46 μg/mL. Thus, SNH plays an antitumor role via regulating the apoptosis, autophagy, and migration of MCF-7 cells, and might act as a potential alternative drug in the treatment of breast cancer.