Journal article
Primary and Liver Metastasis-Derived Cell Lines From KrasG12D; Trp53R172H; Pdx-1 Cre Animals Undergo Apoptosis in Response to Triptolide
Pancreas, Vol.44(4), pp.583-589
05/01/2015
DOI: 10.1097/mpa.0000000000000317
PMID: 25875797
Abstract
Objectives: Pancreatic cancer has a 5-year survival rate of less than 5%, partly because of limited chemotherapeutic options, thereby highlighting the need for novel therapies. Triptolide, a diterpene triepoxide that was derived from a Chinese herb, has shown great promise in preclinical testing against pancreatic cancer using immunocompromised animals.
Results: In this study, we tested the ability of triptolide to induce cell death in cell lines derived from a primary tumor and adjacent liver metastases of immunocompetent animals (Kras(G12D), Trp53(R172H), Pdx-1 Cre [KPC]). Both cell lines were more aggressive in their ability to form tumors when compared with other pancreatic cancer cell lines and showed constitutive activation of the nuclear factor.-light-chain-enhancer of activated B cells pathway. Triptolide induced apoptotic cell death in both cell lines, as evidenced by decreased cell viability as well as increased caspase 3/7 activity, annexin V positivity, and increased terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling positivity in tumors from KPC animals treated with Minnelide. In addition, triptolide decreased levels of HSP70, its transcription factor HSF1, as well as the antiapoptotic proteins Bcl-xL, Bcl-2, and Mcl-1, which are known to be up-regulated in pancreatic cancer.
Conclusions: The ability of triptolide to cause cell death in cell lines derived from immunocompetent animals further validates its potential as a novel agent against pancreatic cancer.
Details
- Title: Subtitle
- Primary and Liver Metastasis-Derived Cell Lines From KrasG12D; Trp53R172H; Pdx-1 Cre Animals Undergo Apoptosis in Response to Triptolide
- Creators
- Veena Sangwan - University of MinnesotaSulagna Banerjee - University of MinnesotaKelsey M. Jensen - University of MinnesotaZhiyu Chen - University of MinnesotaRohit Chugh - University of MinnesotaVikas Dudeja - University of MinnesotaSelwyn M. Vickers - University of MinnesotaAshok K. Saluja - University of Minnesota
- Resource Type
- Journal article
- Publication Details
- Pancreas, Vol.44(4), pp.583-589
- DOI
- 10.1097/mpa.0000000000000317
- PMID
- 25875797
- NLM abbreviation
- Pancreas
- ISSN
- 0885-3177
- eISSN
- 1536-4828
- Publisher
- Lippincott Williams & Wilkins
- Number of pages
- 7
- Grant note
- Masonic Cancer Center P50 CA101955 / University of Alabama Pancreatic Cancer Specialized Programs of Research Excellence grant Department of Surgery R01CA124723; R01CA170496 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Hirshberg Foundation Katherine and Robert Goodale Foundation
- Language
- English
- Date published
- 05/01/2015
- Academic Unit
- Anatomy and Cell Biology; Surgery
- Record Identifier
- 9985244674402771
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