Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P42345 (mTOR)
 26,049 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Our previous study showed that By-1, a maleimide derivative isolated from Taiwanofungus camphoratus, could induce reactive oxygen species-triggered apoptosis and G2 cell cycle arrest through a caspase-dependent pathway and also induced protective autophagy in human lung cancer SPCA-1 cells. Here, we further examined the autophagy flux and detected related proteins by Western blot analysis and fluorescence activated cell sorting, and we sought to find the exact role and underlying pathway of autophagy in SPCA-1 cells. Our results showed that By-1 treatment activated autophagy flux in SPCA-1 cells, which further confirmed that autophagy was induced by By-1 treatment in our previous study. Autophagy activator rapamycin restored cell death from By-1 treatment (21.32%) and verified that autophagy played a protective role in By-l-treated cells. Meanwhile, By-1 treatment suppressed the Akt-mammalian target of rapamycin (mTOR) pathway and the AMP-activated protein kinase (AMPK) pathway. Taken together, these findings indicate that By-1 induced protective autophagy in SPCA-1 cells through AMPK inhibition-independent blockade of the Akt/mTOR pathway.
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PMID:Compound of Stout Camphor Medicinal Mushroom, Taiwanofungus camphoratus (Agaricomycetes), Induces Protective Autophagy in SPCA-1 Cells through AMPK Inhibition-Independent Blockade of the Akt/mTOR Pathway. 3031 49

The current study aims to explore the possible anti-lung carcinoma activity of ADC as well as the underlying mechanisms by which ADC exerts its actions in NSCLC. Findings showed that ADC potently inhibited the viability of SPCA-1, induced apoptosis triggered by ROS, and arrested the cell cycle at the G2/M phase via a P53 signaling pathway. Interestingly, phenomena such as autophagosomes accumulation, conversion of the LC3-I to LC3-II, etc., indicated that autophagy could be activated by ADC. The blockage of autophagy-augmented ADC induced inhibition of cell proliferation, while autophagy activation restored cell death, indicating that autophagy had a protective effect against cell death which was induced by ADC treatment. Meanwhile, ADC treatment suppressed both the Akt/mTOR and AMPK signaling pathways. The joint action of both ADC and the autophagy inhibitor significantly increased the death of SPCA-1. An in vitro phase I metabolic stability assay showed that ADC was highly metabolized in SD rat liver microsomes and moderately metabolized in human liver microsomes, which will assist in predicting the outcomes of clinical pharmacokinetics and toxicity studies. These findings imply that blocking the Akt/mTOR signaling pathway, which was independent of AMPK inhibition, could activate ADC-induced protective autophagy in non-small-cell lung cancer cells.
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PMID:Antrodin C, an NADPH Dependent Metabolism, Encourages Crosstalk between Autophagy and Apoptosis in Lung Carcinoma Cells by Use of an AMPK Inhibition-Independent Blockade of the Akt/mTOR Pathway. 3087 Sep 98