ArticleTumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine2015
The small-molecule compound BM-1197 inhibits the antiapoptotic regulators Bcl-2/Bcl-xL and triggers apoptotic cell death in human colorectal cancer cells.
Article in Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12 citing papers in PubMed, 22 citations in OpenAlex.
- Targeting Bcl-2 with Indole Scaffolds: Emerging Drug Design Strategies for Cancer Treatment.Mini reviews in medicinal chemistry · 2025Review
- Norcantharidin triggers apoptotic cell death in non-small cell lung cancer via a mitophagy-mediated autophagy pathway.Annals of translational medicine · 2021Article
- Targeting apoptosis in cancer therapy.Nature reviews. Clinical oncology · 2020Review
- Inhibition of Anti-Apoptotic Bcl-2 Proteins in Preclinical and Clinical Studies: Current Overview in Cancer.Cells · 2020Review
- Suppression of miR-21-3p enhances TRAIL-mediated apoptosis in liver cancer stem cells by suppressing the PI3K/Akt/Bad cascade via regulating PTEN.Cancer management and research · 2019Article
- Suppression of Notch1 and AKT mediated epithelial to mesenchymal transition by Verrucarin J in metastatic colon cancer.Cell death & disease · 2018Article
- Novel smac mimetic APG-1387 elicits ovarian cancer cell killing through TNF-alpha, Ripoptosome and autophagy mediated cell death pathway.Journal of experimental & clinical cancer research : CR · 2018Article
- miR-217 regulates tumor growth and apoptosis by targeting the MAPK signaling pathway in colorectal cancer.Oncology letters · 2016Article
- Locked nucleic acid inhibits miR-92a-3p in human colorectal cancer, induces apoptosis and inhibits cell proliferation.Cancer gene therapy · 2016Article
- BH3-mimetic small molecule inhibits the growth and recurrence of adenoid cystic carcinoma.Oral oncology · 2015Article
- Apoptosis of human pancreatic carcinoma cell-1 cells induced by Yin Chen Hao Decoction.World journal of gastroenterology · 2015Article
- Identification of potential glucocorticoid receptor therapeutic targets in multiple myeloma.Nuclear receptor signaling · 2015Article
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10 authors at 3 institutions in 1 country.
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Abstract
Small molecule BH3 mimetics comprise a promising new chemotherapeutic strategy for treating relapsed or chemoresistant cancer. In this study, we investigated the cellular mechanism of action by which BM-1197, a Bcl-xL/Bcl-2 dual inhibitor, triggers apoptosis in a panel of colorectal cancer (CRC) lines. Using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, we determined that BM-1197 inhibited CRC cell growth in a concentration- and time-dependent manner. The 50 % inhibitory concentration (IC50) values for the most sensitive cell lines, SW620 and SW480, ranged from 0.07 to 1.10 μM in response to a 72-h treatment. In CRC cells, BM-1197 induced apoptotic death without affecting the expression of Bcl-2 family proteins. However, BM-1197 effectively triggered a conformational change in Bax, releasing Bim from Bcl-xL by disrupting the interaction between Bcl-xL and Bak/Bax. Compared with the control group, BM-1197 treatment significantly increased the fraction of SW480 cells in the sub-G1 phase, the apoptosis rate, and cellular internucleosomal DNA fragmentation. The proapoptotic activity was associated with cytochrome c release, caspase-3 activation, and PARP-1 cleavage. Collectively, BM-1197 effectively suppressed the growth of the human CRC cell line SW480 by inducing mitochondria-dependent apoptotic cell death. These data have specific implications for the in vivo analysis and clinical evaluation of BM-1197 in CRC.
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