Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.11 (AMPK)
 12,425 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intraarticular fibrosis following knee surgery is a troublesome complication and remains a challenging problem for clinicians. Artesunate (ART), a classical anti-malarial drug extracted from the Chinese medicinal herb Artemisia annua L, has been associated with some fibrosis-related diseases. However, its effect and underlying mechanism on knee arthrofibrosis are still obscure. In the present study, we found that ART induced cellular autophagy flux and inhibited cell proliferation in fibroblasts. Intriguingly, genetic depletion of Beclin-1 abolished ART-triggered cellular autophagy and further attenuated the inhibitory effect of ART on fibroblasts proliferation. Moreover, at molecular level, our results demonstrated that ART-induced autophagy activation was associated with the inhibition of mTOR signaling through PI3K/AKT/mTOR pathway and AMPK/mTOR pathway. In vivo, ART treatment triggered autophagy activation and alleviated the severity of surgery-induced knee arthrofibrosis. Taken together, we concluded that ART exhibited anti-proliferation efficacy in fibroblasts and alleviated the severity of knee arthrofibrosis in rabbits by inducing Beclin-1-mediated autophagy via inhibition of mTOR signaling. These findings indicated that ART might be a potential therapeutic agent for preventing the progression of surgery-induced intraarticular fibrosis of knee.
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PMID:Artesunate protects against surgery-induced knee arthrofibrosis by activating Beclin-1-mediated autophagy via inhibition of mTOR signaling. 3099 37

Although mitochondrial metabolism has recently gained attention as a promising therapeutic strategy in cancer, little is known on the impact of mitochondrial respiration inhibition on oral tongue squamous cell carcinoma (OTSCC). Using in vitro and in vivo OTSCC models, our work demonstrates that inducing mitochondrial dysfunction by anti-malarial drug artesunate is effective in targeting OTSCC stem-cell like and bulk cells. Artesunate inhibits anchorage-independent colony formation, proliferation and survival in all tested OTSCC cell lines although with varying efficacy. Artesunate displays preferential anti-OTSCC activity by sparing normal cells. Mechanism analysis indicates that artesunate inhibits mitochondrial respiration via suppressing mitochondrial complex I and II but not IV or V, resulting in oxidative stress and damage. Interestingly, OTSCC cells that are more sensitive to artesunate have higher level of basal mitochondrial respiration and reversed respiratory capacity compared to those with less sensitivity to artesunate, suggesting the varying dependence on mitochondrial respiration among OTSCC cell lines. In addition, artesunate induces oxidative stress and damage in cells with low sensitivity to a less extent than in those with high sensitivity. We confirm that mitochondrial respiration inhibition is required for the action of artesunate in OTSCC. Mitochondrial dysfunction by artesunate further activates AMPK and suppresses Akt/mTOR. Importantly, the in vitro observations are reproducible in vivo OTSCC xenograft mouse model. Our findings provide pre-clinical evidence on the efficacy of artesunate and emphasize the therapeutic value of targeting mitochondrial respiration in OTSCC.
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PMID:Artesunate targets oral tongue squamous cell carcinoma via mitochondrial dysfunction-dependent oxidative damage and Akt/AMPK/mTOR inhibition. 3196 56

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