Houttuynia cordata Thunb Promotes Activation of HIF-1A-FOXO3 and MEF2A Pathways to Induce Apoptosis in Human HepG2 Hepatocellular Carcinoma Cells
INTEGRATIVE CANCER THERAPIES
Authors: Kim, Jung Min; Hwang, In-Hu; Jang, Ik-Soon; Kim, Min; Bang, In Seok; Park, Soo Jung; Chung, Yun-Jo; Joo, Jong-Cheon; Lee, Min-Goo
Abstract
Houttuynia cordata Thunb (H cordata), a medicinal plant, has anticancer activity, as it inhibits cell growth and induces cell apoptosis in cancer. However, the potential anti-cancer activity and mechanism of H cordata for human liver cancer cells is not well understood. Recently, we identified hypoxia-inducible factor (HIF)-1A, Forkhead box (FOX)O3, and MEF2A as proapoptotic factors induced by H cordata, suggesting that HIF-1A, FOXO3, and MEF2A contribute to the apoptosis of HepG2 hepatocellular carcinoma cells. FOXO3 transcription factors regulate target genes involved in apoptosis. H cordata significantly increased the mRNA and protein expression of HIF-1A and FOXO3 and stimulated MEF2A expression in addition to increased apoptosis in HepG2 cells within 24 hours. Therefore, we determined the potential role of FOXO3 on apoptosis and on H cordata-induced MEF2A in HepG2 cells. HIF-1A silencing by siRNA attenuated MEF2A and H cordata-mediated FOXO3 upregulation in HepG2 cells. Furthermore, H cordata-mediated MEF2A expression enhanced caspase-3 and caspase-7, which were abolished on silencing FOXO3 with siRNA. In addition, H cordata inhibited growth of human hepatocellular carcinoma xenografts in nude mice. Taken together, our results demonstrate that H cordata enhances HIF-1A/FOXO3 signaling, leading to MEF2A upregulation in HepG2 cells, and in parallel, it disturbs the expression of Bcl-2 family proteins (Bax, Bcl-2, and Bcl-xL), which results in apoptosis. Taken together, these findings demonstrate that H cordata promotes the activation of HIF-1A-FOXO3 and MEF2A pathways to induce apoptosis in human HepG2 hepatocellular carcinoma cells and is, therefore, a promising candidate for antitumor drug development.
The Change of Interleukin-6 Level-Related Genes and Pathways Induced by Exercise in Sedentary Individuals
JOURNAL OF INTERFERON AND CYTOKINE RESEARCH
Authors: Chen, Lei; Bai, Jun; Li, Yanfei
Abstract
Sedentary behavior increases the risk of many chronic disorders, in addition, these chronic diseases are associated with elevated markers interleukin-6 (IL-6). Increasing evidence indicates that physical activity can prevent chronic inflammatory disease. However, the effect of exercise on sedentary individuals with disparate basal serum IL-6 level was not well elucidated. In this study, the gene expression profile of GES12384 was downloaded from the Gene Expression Omnibus (GEO) database. This data set contained 12 sedentary middle-aged men (6 high IL-6 and 6 low IL-6 level), and their blood samples were taken in the pre-exercise period and at the end of 24 weeks of exercise. The differentially expressed genes (DEGs) of 24 weeks group were identified, followed by functional enrichment analysis. Subsequently, protein-protein interaction (PPI) network and transcription factors (TFs)-DEGs network were constructed. A total of 193 DEGs were identified between high and low IL-6 level in the 24 weeks group. Functional enrichment analysis showed that DEGs were mainly involved in African trypanosomiasis pathway. PPI network revealed that the hub genes included C-C motif chemokine receptor 7 (CCR7), hemoglobin subunit delta (HBD), and interferon gamma (IFNG). Subnetworks analysis indicated that these genes were relevant to immune response, and participated in African trypanosomiasis pathway. The TF targets network found that myocyte enhancer factor 2A (MEF2A) was a key regulatory factor. In conclusion, the inflammation-related genes (CCR7, HBD, and IFNG) in sedentary individuals could be affected by exercise, and the identified DEGs and TFs in this study promoted our understanding of exercise inhibited the development of chronic disease. [GRAPHICS] .