ArticleOncoscience2015
Sorafenib induces cathepsin B-mediated apoptosis of bladder cancer cells by regulating the Akt/PTEN pathway. The Akt inhibitor, perifosine, enhances the sorafenib-induced cytotoxicity against bladder cancer cells.
Article in Oncoscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 28 citations in OpenAlex.
- Sorafenib/piroxicam therapy with biomarker-defined survival benefit in canine muscle-invasive urothelial carcinoma.Scientific reports · 2026Article
- Clomipramine potentiates sorafenib efficacy in experimental hepatocellular carcinoma by targeting lysosomal sequestration and modulating the cathepsin B/Bcl-2/Beclin-1 axis.Molecular biology reports · 2026Article
- Exploring potential VEGF receptor 2 inhibitors: a molecular modeling and pharmacophore-based screening approach.Scientific reports · 2026Article
- Research progress on the role of AGC kinase family in bladder cancer.Discover oncology · 2025Review
- The Potential of Congo Red Supplied Aggregates of Multitargeted Tyrosine Kinase Inhibitor (Sorafenib, BAY-43-9006) in Enhancing Therapeutic Impact on Bladder Cancer.International journal of molecular sciences · 2023Article
- Helicobacter pylori and gastric cancer: a lysosomal protease perspective.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2022Review
- Effects of Sorafenib and Arsenic Trioxide on U937 and KG-1 Cell Lines: Apoptosis or Autophagy?Cell journal · 2020Article
- Typical and Atypical Inducers of Lysosomal Cell Death: A Promising Anticancer Strategy.International journal of molecular sciences · 2018Review
- Dysfunction of Membrane Trafficking Leads to Ischemia-Reperfusion Injury After Transient Cerebral Ischemia.Translational stroke research · 2018Review
- Sorafenib tosylate inhibits directly necrosome complex formation and protects in mouse models of inflammation and tissue injury.Cell death & disease · 2017Article
- A simple method to induce hypoxia-induced vascular endothelial growth factor-A (VEGF-A) expression in T24 human bladder cancer cells.In vitro cellular & developmental biology. Animal · 2017Article
- RETRACTED: Myogenic differentiation of VCP disease-induced pluripotent stem cells: A novel platform for drug discovery.PloS one · 2017Article
- Article
- Synergistic effect of fisetin combined with sorafenib in human cervical cancer HeLa cells through activation of death receptor-5 mediated caspase-8/caspase-3 and the mitochondria-dependent apoptotic pathway.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Melatonin combined with sorafenib synergistically inhibit the invasive ability through targeting metastasis-associated protein 2 expression in human renal cancer cells.Tzu chi medical journalArticle
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sorafenib, a tyrosine kinase inhibitor, has been demonstrated to exert anti-tumor effects. However, the molecular mechanisms underlying its effects on bladder cancer remain unknown. Here, we evaluated the mechanisms responsible for the sorafenib-induced anti-tumor effects on 5637 and T24 bladder cancer cells. We demonstrated that sorafenib reduces cell viability, stimulates lysosome permeabilization and induces apoptosis of bladder cancer cells. These effects are dependent by the activation of cathepsin B released from lysosomes. The sorafenib-increased cathepsin B activity induced the proteolysis of Bid into tBid that stimulates the intrinsic pathway of apoptosis characterized by mitochondrial membrane depolarization, oxygen radical generation and cytochrome c release. Moreover, we found that cathepsin B enzymatic activity, induced by sorafenib, is dependent on its dephosphorylation via PTEN activation and Akt inactivation. Pretreatment with orthovanadate rescued bladder cancer cells from apoptosis. In addition, the Akt inhibitor perifosine increased the sensitivity of bladder cancer cells to sorafenib-induced cytotoxicity. Overall, our results show that apoptotic cell death induced by sorafenib in bladder cancer cells is dependent on cathepsin B activity and involved PTEN and Akt signaling pathways. The Akt inhibitor perifosine increased the cytotoxic effects of sorafenib in bladder cancer cells.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.