Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dioscin shows various pharmacological effects. However, its activity on colorectal cancer is still unknown. The present work showed that dioscin significantly inhibited cell proliferation on human HCT-116 colon cancer cells, and affected Ca(2+) release and ROS generation. The content of nitric oxide (NO) and its producer inducible NO synthase (iNOS) associated with DNA damage and aberrant cell signaling were assayed using the kits. DNA damage and cell apoptosis caused by dioscin were also analyzed through single-cell gel electrophoresis and in situ terminal deoxynucleotidyl transferase dUTP nick-end labeling assays. The results showed that dioscin increased the levels of NO and inducible NO synthase. The comet length in dioscin-treated groups was much longer than that of the control group, and the number of terminal deoxynucleotidyl transferase dUTP nick-end labeling positive cells (apoptotic cells) was significantly increased by the compound (p < 0.01). Furthermore, dioscin caused mitochondrial damage and G2/M cell cycle arrest through transmission electron microscopy and flow cytometry analysis, respectively. To study the cytotoxic mechanism of dioscin, an iTRAQ-based proteomics approach was used. There were 288 significantly different proteins expressed in response to dioscin, which were connected with each other and were involved in different Kyoto Encyclopedia of Genes and Genomes pathways. Then, some differentially expressed proteins involved in oxidative phosphorylation, Wnt, p53, and calcium signaling pathways were validated by Western blotting and quantitative real-time PCR assays. Our work elucidates the molecular mechanism of dioscin-induced cytotoxicity in colon cancer cells, and the identified targets may be useful for treatment of colorectal cancer in future.
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PMID:iTRAQ-based proteomic analysis of dioscin on human HCT-116 colon cancer cells. 2442 Sep 67

Dioscin, a natural product, has activity against glioblastoma multiforme, lung cancer and colon cancer. In this study, the effects of dioscin against human cervical carcinoma HeLa and SiHa cells were further confirmed, and the possible mechanism(s) were investigated. A transmission electron microscopy (TEM) assay and DAPI staining were used to detect the cellular morphology. Flow cytometry was used to assay cell apoptosis, ROS and Ca(2+) levels. Single cell gel electrophoresis and immunofluorescence assays were used to test DNA damage and cytochrome C release. The results showed that dioscin significantly inhibited cell proliferation and caused DNA damage in HeLa and SiHa cells. The mechanistic investigation showed that dioscin caused the release of cytochrome C from mitochondria into the cytosol. In addition, dioscin significantly up-regulated the protein levels of Bak, Bax, Bid, p53, caspase-3, caspase-9, and down-regulated the protein levels of Bcl-2 and Bcl-xl. Our work thus demonstrated that dioscin notably induces apoptosis in HeLa and SiHa cells through adjusting ROS-mediated DNA damage and the mitochondrial signaling pathway.
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PMID:Dioscin Induces Apoptosis in Human Cervical Carcinoma HeLa and SiHa Cells through ROS-Mediated DNA Damage and the Mitochondrial Signaling Pathway. 3193 56

Dioscin is a natural steroid saponin derived from several plants that shows potent anticancer effects against a variety of cancer cells. Here, we investigated the antitumor effect of dioscin against human colon cancer cells and evaluated the molecular mechanism involved in this process. The cell cytotoxicity was studied by the MTT assay and BrdU incorporation. The proapoptotic mechanism of dioscin was characterized by flow cytometry analysis. A western blot and an immunofluorescence staining were used to investigate how dioscin induces apoptosis in vitro. In our study, dioscin could significantly inhibit the growth of colon cancer cells in a time-dependent and dose-dependent manner. Dioscin induces apoptosis and reactive oxygen species (ROS) generation, promoting the disruption of mitochondrial membrane potential, Bax translocation to the mitochondria, cytochrome C release to cytosol, activations of caspase-9/3, PARP cleavage, and subsequent apoptosis. Dioscin-induced apoptosis was accompanied by sustained phosphorylation of JNK, p38-MAPK. N-acetyl-L-cysteine, a scavenger of ROS, significantly reversed dioscin-induced cell death and activation of JNK and p38. Collectively, the data indicate that the induction of apoptosis by dioscin is mediated through ROS proteins, which are critical upstream signals for JNK/p38-MAPK activation.
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PMID:Dioscin inhibits colon cancer cells' growth by reactive oxygen species-mediated mitochondrial dysfunction and p38 and JNK pathways. 2938 2