ArticleThe Journal of biological chemistry2008
Anti-cancer effects of JKA97 are associated with its induction of cell apoptosis via a Bax-dependent and p53-independent pathway.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 35 citations in OpenAlex.
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- Alkaloids and Colon Cancer: Molecular Mechanisms and Therapeutic Implications for Cell Cycle Arrest.Molecules (Basel, Switzerland) · 2022Review
- Thymoquinone Selectively Induces Hepatocellular Carcinoma Cell Apoptosis in Synergism With Clinical Therapeutics and Dependence of p53 Status.Frontiers in pharmacology · 2020Article
- MicroRNA-411 Downregulation Enhances Tumor Growth by Upregulating MLLT11 Expression in Human Bladder Cancer.Molecular therapy. Nucleic acids · 2018Article
- Transcriptional and post-transcriptional upregulation of p27 mediates growth inhibition of isorhapontigenin (ISO) on human bladder cancer cells.Carcinogenesis · 2018Article
- A Conserved Splicing Silencer Dynamically Regulates O-GlcNAc Transferase Intron Retention and O-GlcNAc Homeostasis.Cell reports · 2017Article
- Role of STAT3 and FOXO1 in the Divergent Therapeutic Responses of Non-metastatic and Metastatic Bladder Cancer Cells to miR-145.Molecular cancer therapeutics · 2017Article
- XIAP BIR domain suppresses miR-200a expression and subsequently promotes EGFR protein translation and anchorage-independent growth of bladder cancer cell.Journal of hematology & oncology · 2017Article
- Synthesis and mechanisms of action of novel harmine derivatives as potential antitumor agents.Scientific reports · 2016Article
- Isorhapontigenin (ISO) inhibited cell transformation by inducing G0/G1 phase arrest via increasing MKP-1 mRNA Stability.Oncotarget · 2014Article
- The Chinese herb isolate yuanhuacine (YHL-14) induces G2/M arrest in human cancer cells by up-regulating p21 protein expression through an p53 protein-independent cascade.The Journal of biological chemistry · 2014Article
- SUMOylation of RhoGDIα is required for its repression of cyclin D1 expression and anchorage-independent growth of cancer cells.Molecular oncology · 2014Article
- S100A14, a member of the EF-hand calcium-binding proteins, is overexpressed in breast cancer and acts as a modulator of HER2 signaling.The Journal of biological chemistry · 2014Article
- X-linked inhibitor of apoptosis protein (XIAP) regulation of cyclin D1 protein expression and cancer cell anchorage-independent growth via its E3 ligase-mediated protein phosphatase 2A/c-Jun axis.The Journal of biological chemistry · 2013Article
- GADD45β mediates p53 protein degradation via Src/PP2A/MDM2 pathway upon arsenite treatment.Cell death & disease · 2013Article
- The Chinese herb isolate isorhapontigenin induces apoptosis in human cancer cells by down-regulating overexpression of antiapoptotic protein XIAP.The Journal of biological chemistry · 2012Article
- Article
- X-linked inhibitor of apoptosis protein (XIAP) mediates cancer cell motility via Rho GDP dissociation inhibitor (RhoGDI)-dependent regulation of the cytoskeleton.The Journal of biological chemistry · 2011Article
- Harmine activates intrinsic and extrinsic pathways of apoptosis in B16F-10 melanoma.Chinese medicine · 2011Article
- Enhancement of temozolomide-induced apoptosis by valproic acid in human glioma cell lines through redox regulation.Journal of molecular medicine (Berlin, Germany) · 2011Article
Corrections and comments
- Erratum issued
Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
p53, one of the most commonly mutated genes in human cancers, is thought to be associated with cancer development. Hence, screening and identifying natural or synthetic compounds with anti-cancer activity via p53-independent pathway is one of the most challenging tasks for scientists in this field. Compound JKA97 (methoxy-1-styryl-9H-pyrid-[3,4-b]-indole) is a small molecule synthetic anti-cancer agent, with unknown mechanism(s). In this study we have demonstrated that the anti-cancer activity of JKA97 is associated with apoptotic induction via p53-independent mechanisms. We found that co-incubation of human colon cancer HCT116 cells with JKA97 inhibited HCT116 cell anchorage-independent growth in vitro and tumorigenicity in nude mice and also induced a cell apoptotic response, both in the cell culture model and in a tumorigenesis nude mouse model. Further studies showed that JKA97-induced apoptosis was dramatically impaired in Bax knock-out (Bax(-/-)) HCT116 cells, whereas the knock-out of p53 or PUMA did not show any inhibitory effects. The p53-independent apoptotic induction by JKA97 was confirmed in other colon cancer and hepatocarcinoma cell lines. In addition, our results showed an induction of Bax translocation and cytochrome c release from the mitochondria to the cytosol in HCT116 cells, demonstrating that the compound induces apoptosis through a Bax-initiated mitochondria-dependent pathway. These studies provide a molecular basis for the therapeutic application of JKA97 against human cancers with p53 mutations.
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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.