Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.60 (caspase-7)
 920 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Houttuynia cordata Thunb Promotes Activation of HIF-1A-FOXO3 and MEF2A Pathways to Induce Apoptosis in Human HepG2 Hepatocellular Carcinoma Cells. 2769 66

This study was focused on investigating the anticancer potential of indole-3-carbinol (I3C) against osteosarcoma MG-63 and U2OS cells. A wound healing assay indicated that IC3 inhibited migration of MG-63 and U2OS cells. MTT, WST-1, and colony formation assays revealed that treatment of MG-63 and U2OS cells with I3C decreased cell viability. Fluorescence-activated cell sorting (FACS) analysis showed that I3C induced apoptosis in a dose- and time-dependent manner in MG-63 and U2OS cells. Moreover, via terminal deoxynucleotidyl transferase- (TdT-) mediated dUTP-biotin nick-end labeling (TUNEL) assay, we detected that I3C induced DNA fragmentation. Western blotting demonstrated that activated forms of caspase-3, caspase-7, and caspase-9, as well as poly (ADP-ribose) polymerase (PARP) were increased in MG-63 and U2OS cells, following treatment with I3C. Furthermore, protein expression levels of FOXO3, Bax, and Bim extra-large form were increased while those of Akt, JNK, p38, phosphorylated ERK, and Bcl-xL were decreased by I3C treatment in MG-63 and U2OS cells. Thus, the study indicates that I3C may induce apoptosis in human osteosarcoma MG-63 and U2OS cells via the activation of apoptotic signaling pathways by FOXO3.
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PMID:Indole-3-Carbinol Induces Apoptosis in Human Osteosarcoma MG-63 and U2OS Cells. 3062 73

This study was focused on investigating the anticancer potential of indole-3-carbinol (I3C) against lung cancer H1299 cells via an increase in ROS levels. To investigate the induction of growth arrest and/or cell death in H1299 cells, a cell cycle arrest assay, terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick-end labeling (TUNEL) assay, and reactive oxygen species (ROS) detection assay were performed. Through the TUNEL assay, we detected I3C-induced DNA fragmentation. Fluorescence-activated cell sorting (FACS) analysis showed that I3C induced an increase in ROS levels and apoptotic rate in a dose- and time-dependent manner in H1299 cells. Western blotting demonstrated that activated forms of caspase-3, caspase-7, caspase-9, and poly (ADP-ribose) polymerase (PARP) were increased in I3C-treated H1299 cells following treatment with I3C. Furthermore, protein expression levels of FOXO3, bim, bax, and phosphorylated ERK and JNK were increased, while those of pAkt, Bcl-xL, and Bcl-2 were decreased by I3C treatment of H1299 cells. To confirm the relationship between cell apoptosis and ROS generation, H1299 cells were treated with I3C simultaneously with N-acetylcysteine (NAC), and it was shown that ROS levels decreased and viability increased. Moreover, in western blot analysis, expression of anti-apoptotic proteins (thioredoxin1, peroxiredoxin-1, Bcl-2, and Bcl-xL) in I3C-treated cells was evidently downregulated and pro-apoptotic proteins (active ASK1 and cleaved PARP) were upregulated compared to cells co-treated with NAC. The study showed that I3C induced downregulation of ROS regulator proteins and elevation of ROS, thus activating apoptotic signaling cascades in human lung cancer H1299 cells.
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PMID:Induction of apoptosis in indole-3-carbinol-treated lung cancer H1299 cells via ROS level elevation. 3311 90