Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0005684 (bladder cancer)
 16,431 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bladder cancer is the most common malignant tumor of the urinary tract and remains one of the major causes of cancer death worldwide. In this study, we investigated the effect and mechanism of Artesunate (ART), a traditional Chinese medicine, on inducing apoptosis of human bladder cancer cells. In vivo antitumor activity was investigated in bladder cancer in rat by subcutaneous injection of different concentration of ART. The effect of ART on growth inhibition and apoptosis of bladder cancer cells was evaluated using dimethylthiazoly-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry analysis, respectively. Cyclooxygenase-2 (COX-2) and miR-16 expression levels were determined with real-time PCR. The concentrations of prostaglandin E2 (PGE2) in the supernatants of bladder cancer cells were measured with an ELISA kit. The miR-16 inhibitor or mimic were transfected into cells to up- or down-regulate miR-16 expression. ART efficiently inhibited orthotopic tumor growth in the bladder cancer rat, which is accompanied with an increase of miR-16 expression and a decrease of COX-2 expression. In vitro, ART could induce cytotoxicity and apoptosis in bladder cancer cells, but presented a much lighter toxicity effect against normal human urothelial cells. ART significantly increased miR-16 expression and decreased the expression of COX-2 and the production of PGE2. More importantly, down-regulation of miR-16 expression could reverse the effect of ART on apoptosis and COX-2 expression in bladder cells. Moreover, exogenous PGE2 could inhibit apoptosis of bladder cancer cells treated with ART. In conclusion, ART can elicit an anti-tumor effect against bladder cancer by up-regulation of miR-16 expression, which resulted in the decrease of COX-2 expression and PGE2 production. Hence, ART might be an effective drug for the treatment of bladder cancer.
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PMID:Artesunate induces apoptosis of bladder cancer cells by miR-16 regulation of COX-2 expression. 2519 24

Artesunate is a kind of derivative of artemisinin, which possesses potent anti-cancer effect in addition to its anti-malarial property. And autophagy was a highly conserved process, exerting a double-edged effect in cancer cell survival. Besides, apoptosis is a programmed cell death program, crucial to cell homeostasis. However, the relations between autophagy and apoptosis, and the role of artesunate in this interaction have not been elucidated in bladder cancer. In present study, we used human bladder cancer cells (T24 and EJ cell lines) to investigate that how artesunate would influence autophagy and apoptosis processes. We found that artesunate could inhibit the viability, proliferation and migration of bladder cancer cells, as well as induce autophagy in a time and dose dependent manner, in addition, the artesunate induced autophagy subsequently activated cells apoptosis. Furthermore, we pretreated T24 and EJ cells with 3-Methyladenine or Rapamycin to inhibit or promote autophagy, respectively, leading to inhibited or increased apoptosis. Moreover, pretreatment of these cell lines with Acadesine or Dorsomorphin to activate or inhibit the AMPK-mTOR-ULK1 pathway, respectively, also resulting in promotion or suppression in both autophagy and apoptosis. In the upstream, ROS upregulation triggered by ART initiated AMPK-mTOR-ULK1 axis. However, this initiative effect of ROS can be reversed by N-Acetyl-l-cysteine. Therefore, this study indicated that Artesunate induces autophagy dependent apoptosis through upregulating ROS and activating AMPK-mTOR-ULK1 pathway in human bladder cancer cells.
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PMID:Artesunate induces autophagy dependent apoptosis through upregulating ROS and activating AMPK-mTOR-ULK1 axis in human bladder cancer cells. 3300 60