M1190 5-Aminosalicylic Acid Induces Colorectal Cancer Cell Death In Vitro and In Vivo

The deregulation of the Wnt/β-catenin signaling pathway is a central event in colorectal cancer progression, thus a promising target for drug development. Many natural compounds, such as flavonoids, have been described as Wnt/β-catenin inhibitors and consequently modulate important biological processes like inflammation, redox balance, cancer promotion and progress, as well as cancer cell death. In this context, we identified the chalcone lonchocarpin isolated from Lonchocarpus sericeus as a Wnt/β-catenin pathway inhibitor, both in vitro and in vivo. Lonchocarpin impairs β-catenin nuclear localization and also inhibits the constitutively active form of TCF4, dnTCF4-VP16. Xenopus laevis embryology assays suggest that lonchocarpin acts at the transcriptional level. Additionally, we described lonchocarpin inhibitory effects on cell migration and cell proliferation on HCT116, SW480, and DLD-1 colorectal cancer cell lines, without any detectable effects on the non-tumoral intestinal cell line IEC-6. Moreover, lonchocarpin reduces tumor proliferation on the colorectal cancer AOM/DSS mice model. Taken together, our results support lonchocarpin as a novel Wnt/β-catenin inhibitor compound that impairs colorectal cancer cell growth in vitro and in vivo.

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The CDK4/6 inhibitor palbociclib synergizes with irinotecan to promote colorectal cancer cell death under hypoxia

Cell Cycle ◽

10.1080/15384101.2017.1320005 ◽

2017 ◽

Vol 16 (12) ◽

pp. 1193-1200 ◽

Cited By ~ 15

Author(s):

Jun Zhang ◽

Lanlan Zhou ◽

Shuai Zhao ◽

David T. Dicker ◽

Wafik S. El-Deiry

Keyword(s):

Colorectal Cancer ◽

Cell Death ◽

Cancer Cell ◽

Colorectal Cancer Cell ◽

Cancer Cell Death

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Involvement of general control nonderepressible kinase 2 in cancer cell apoptosis by posttranslational mechanisms

Molecular Biology of the Cell ◽

10.1091/mbc.e14-10-1438 ◽

2015 ◽

Vol 26 (6) ◽

pp. 1044-1057 ◽

Cited By ~ 10

Author(s):

Chen Wei ◽

Ma Lin ◽

Bian Jinjun ◽

Feng Su ◽

Cao Dan ◽

...

Keyword(s):

Cell Death ◽

Cancer Cell ◽

Protein Level ◽

Cell Apoptosis ◽

General Control ◽

Screening Assay ◽

Cancer Cell Apoptosis ◽

Cancer Cell Death

General control nonderepressible kinase 2 (GCN2) is a promising target for cancer therapy. However, the role of GCN2 in cancer cell survival or death is elusive; further, small molecules targeting GCN2 signaling are not available. By using a GCN2 level-based drug screening assay, we found that GCN2 protein level critically determined the sensitivity of the cancer cells toward Na+,K+-ATPase ligand–induced apoptosis both in vitro and in vivo, and this effect was largely dependent on C/EBP homologous protein (CHOP) induction. Further analysis revealed that GCN2 is a short-lived protein. In A549 lung carcinoma cells, cellular β-arrestin1/2 associated with GCN2 and maintained the GCN2 protein level at a low level by recruiting the E3 ligase NEDD4L and facilitating consequent proteasomal degradation. However, Na+,K+-ATPase ligand treatment triggered the phosphorylation of GCN2 at threonine 899, which increased the GCN2 protein level by disrupting the formation of GCN2–β-arrestin–NEDD4L ternary complex. The enhanced GCN2 level, in turn, aggravated Na+,K+-ATPase ligand–induced cancer cell apoptosis. Our findings reveal that GCN2 can exert its proapoptotic function in cancer cell death by posttranslational mechanisms. Moreover, Na+,K+-ATPase ligands emerge as the first identified small-molecule drugs that can trigger cancer cell death by modulating GCN2 signaling.

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pH-Triggered burst intracellular release from hollow microspheres to induce autophagic cancer cell death

Journal of Materials Chemistry B ◽

10.1039/c5tb00328h ◽

2015 ◽

Vol 3 (48) ◽

pp. 9383-9396 ◽

Cited By ~ 10

Author(s):

Xin Liang ◽

Ying Yang ◽

Lijun Wang ◽

Xianbing Zhu ◽

Xiaowei Zeng ◽

...

Keyword(s):

Cell Death ◽

Cancer Cell ◽

Hollow Microspheres ◽

Cancer Cell Death ◽

Intracellular Release

Rapamycin–NaHCO3-loaded HMs combined CQ–NaHCO3-loaded HMs could efficiently induce cancer cell death through apoptosis with autophagosome both in vitro and in vivo.

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