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, Trp53, 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 κ-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.
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Authors | Veena Sangwan, Sulagna Banerjee, Kelsey M Jensen, Zhiyu Chen, Rohit Chugh, Vikas Dudeja, Selwyn M Vickers, Ashok K Saluja |
Journal | Pancreas
(Pancreas)
Vol. 44
Issue 4
Pg. 583-9
(May 2015)
ISSN: 1536-4828 [Electronic] United States |
PMID | 25875797
(Publication Type: Evaluation Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents, Alkylating
- Biomarkers, Tumor
- Diterpenes
- Epoxy Compounds
- Phenanthrenes
- triptolide
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Topics |
- Animals
- Antineoplastic Agents, Alkylating
(pharmacology, therapeutic use)
- Apoptosis
(drug effects)
- Biomarkers, Tumor
(metabolism)
- Cell Line, Tumor
- Diterpenes
(pharmacology, therapeutic use)
- Epoxy Compounds
(pharmacology, therapeutic use)
- Immunocompetence
- Mice
- Mice, Transgenic
- Pancreatic Neoplasms
(drug therapy, immunology)
- Phenanthrenes
(pharmacology, therapeutic use)
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