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27.03.2019 | Original Paper

ABT-263 exhibits apoptosis-inducing potential in oral cancer cells by targeting C/EBP-homologous protein

verfasst von: In-Hyoung Yang, Ji-Youn Jung, Sung-Hyun Kim, Eun-Seon Yoo, Nam-Pyo Cho, Hakmo Lee, Jeong-Yeon Lee, Seong Doo Hong, Ji-Ae Shin, Sung-Dae Cho

Erschienen in: Cellular Oncology | Ausgabe 3/2019

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Abstract

Purpose

ABT-263 is a potent BH3 mimetic that possesses anticancer potential against various types of cancer. In general, this potential is due to its high binding affinity to anti-apoptotic proteins in the Bcl-2 family that disrupt sequestration of pro-apoptotic proteins. In the present study, we sought to identify an alternative regulatory mechanism responsible for ABT-263-mediated anticancer activity in human oral cancer.

Methods

We investigated the in vitro anti-cancer effects of ABT-263 using a trypan blue exclusion assay, Western blotting, DAPI staining, immunofluorescence staining, a live/dead assay, microarray-based expression profiling, and quantitative real-time PCR. In vivo anti-tumorigenic effects of ABT-263 were examined using a nude mouse tumor xenograft model, a TUNEL assay, and immunohistochemistry.

Results

We found that ABT-263 suppressed viability and induced apoptosis in human oral cancer-derived cell lines HSC-3 and HSC-4. Subsequent microarray-based gene expression profiling revealed 55 differentially expressed genes in the ABT-263-treatead group, including 12 genes associated with “endoplasmic reticulum stress and apoptosis.” Consistent with the microarray results, the mRNA expression levels of the top four genes (CHOP, TRB3, ASNS, and STC2) were found to be significantly increased. In addition, we found that ABT-263 considerably enhanced the expression levels of the C/EBP-homologous protein (CHOP) and its mRNA, resulting in apoptosis induction in four other human oral cancer-derived cell lines (MC-3, YD-15, HN22, and Ca9.22). Extending our in vitro findings, we found that ABT-263 reduced the growth of HSC-4 cells in vivo at a dosage of 100 mg/kg/day without any change in body weight. TUNEL-positive cells were also found to be increased in tumors of ABT-263-treated mice without any apparent histopathological changes in liver or kidney tissues.

Conclusions

These results provide evidence that ABT-263 may serve as an effective therapeutic agent for the treatment of human oral cancer.

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Titel: ABT-263 exhibits apoptosis-inducing potential in oral cancer cells by targeting C/EBP-homologous protein
verfasst von: In-Hyoung Yang
Ji-Youn Jung
Sung-Hyun Kim
Eun-Seon Yoo
Nam-Pyo Cho
Hakmo Lee
Jeong-Yeon Lee
Seong Doo Hong
Ji-Ae Shin
Sung-Dae Cho
Publikationsdatum: 27.03.2019
Verlag: Springer Netherlands
Erschienen in: Cellular Oncology / Ausgabe 3/2019
Print ISSN: 2211-3428
Elektronische ISSN: 2211-3436
DOI: https://doi.org/10.1007/s13402-019-00431-5

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

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ABT-263 exhibits apoptosis-inducing potential in oral cancer cells by targeting C/EBP-homologous protein

Abstract

Purpose

Methods

Results

Conclusions

Neu im Fachgebiet Pathologie

Assistierter Suizid durch Infusion von Thiopental

Molekularpathologische Untersuchungen im Wandel der Zeit

Vergleichende Pathologie in der onkologischen Forschung

Gastrointestinale Stromatumoren

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusions

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