ArticleThe American journal of pathology2006
Fas-mediated apoptosis in cholangiocarcinoma cells is enhanced by 3,3'-diindolylmethane through inhibition of AKT signaling and FLICE-like inhibitory protein.
Article in The American journal of pathology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- Molecular Targets and Signaling Pathways in Cholangiocarcinoma: A Systematic Review.Asian Pacific journal of cancer prevention : APJCP · 2023Pooled it
- Facile synthesis of indole heterocyclic compounds based micellar nano anti-cancer drugs.RSC advances · 2018Article
- Article
- Characterization of calmodulin-Fas death domain interaction: an integrated experimental and computational study.Biochemistry · 2014Article
- Increased activation of PI3K/AKT signaling pathway is associated with cholangiocarcinoma metastasis and PI3K/mTOR inhibition presents a possible therapeutic strategy.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2013Article
- Targeted regulation of PI3K/Akt/mTOR/NF-κB signaling by indole compounds and their derivatives: mechanistic details and biological implications for cancer therapy.Anti-cancer agents in medicinal chemistry · 2013Review
- PARP-1 regulates resistance of pancreatic cancer to TRAIL therapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2013Article
- Structural and biophysical characterization of the interactions between the death domain of Fas receptor and calmodulin.The Journal of biological chemistry · 2013Article
- Antioxidant function of isoflavone and 3,3'-diindolylmethane: are they important for cancer prevention and therapy?Antioxidants & redox signaling · 2013Review
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- Article
- 3,3'-Diindolylmethane exhibits antileukemic activity in vitro and in vivo through a Akt-dependent process.PloS one · 2012Article
- A study of mifepristone/IFN-γ-induced apoptosis of human cholangiocarcinoma cell line FRH-0201 in vitro.OncoTargets and therapy · 2012Article
- Article
- RETRACTED: Mechanisms and therapeutic implications of cell death induction by indole compounds.Cancers · 2011Article
- Calmodulin mediates Fas-induced FADD-independent survival signaling in pancreatic cancer cells via activation of Src-extracellular signal-regulated kinase (ERK).The Journal of biological chemistry · 2011Article
- Prostate apoptosis response-4 is expressed in normal cholangiocytes, is down-regulated in human cholangiocarcinoma, and promotes apoptosis of neoplastic cholangiocytes when induced pharmacologically.The American journal of pathology · 2010Article
- Activation of checkpoint kinase 2 by 3,3'-diindolylmethane is required for causing G2/M cell cycle arrest in human ovarian cancer cells.Molecular pharmacology · 2010Article
- Chemopreventive agent 3,3'-diindolylmethane selectively induces proteasomal degradation of class I histone deacetylases.Cancer research · 2010Article
- Human cholangiocarcinoma development is associated with dysregulation of opioidergic modulation of cholangiocyte growth.Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver · 2009Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Stimulation of Fas-mediated apoptosis has been promoted as a potential therapy for many cancers, including cholangiocarcinoma. We have previously reported that Fas-resistant, but not Fas-sensitive, cholangiocarcinoma cells are tumorigenic in nude mice. The present studies sought to identify molecular targets that promote Fas-mediated apoptosis in cholangiocarcinoma. We found that Fas-resistant cholangiocarcinoma cells exhibited increased constitutive phosphorylation of AKT compared with Fas-sensitive cells. Increased phosphorylation of AKT was also demonstrated in human cholangiocarcinoma tumors and was evident in a mouse xenograft cholangiocarcinoma model. Furthermore, we found that 3,3'-diindolylmethane (DIM), a vegetable autolysis product, promoted Fas-mediated apoptosis of cholangiocarcinoma cells. DIM inhibited phosphorylation of AKT and activation of FLICE-like-inhibitory-protein (FLIP). Inhibition of phosphatidylinositol 3-kinase/AKT decreased FLIP activation and promoted Fas-mediated apoptosis. By contrast, adenovirus-mediated constitutively activated AKT protected cholangiocarcinoma cells from Fas-mediated apoptosis. Decreased activation of extracellular signal-regulated kinase and nuclear factor-kappaB and increased activation of caspase-3, -8, and -9 were associated with inhibition of AKT and FLIP. These results support AKT and FLIP as potential molecular targets and DIM as a potent compound for cholangiocarcinoma intervention.
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