A novel epigenetic modulating agent sensitizes pancreatic cells to a chemotherapy agent

Pancreatic ductal adenocarcinoma (PDAC) is expected to be the second leading cause of cancer mortality by 2030. PDAC remains resistant to the majority of systemic chemotherapies. In this paper, we explore if epigenetic sensitization can improve chemotherapy response in PDAC. Multiple PDAC cell lines...

Full description

Saved in:
Bibliographic Details
Published in:PloS one 2018-06, Vol.13 (6), p.e0199130-e0199130
Main Authors: Thakar, Manjusha, Hu, Yue, Morreale, Michael, Lerner, Lane, Ying Lin, Wan, Sen, Rupashree, Cai, Yi, Karunasena, Enusha, Thakar, Maya, Saggi, Soren, Keer, Harold, Ahuja, Nita
Format: Article
Language:English
Subjects:
Adenocarcinoma
Antineoplastic Agents - pharmacology
Apoptosis
Azacitidine - analogs & derivatives
Azacitidine - pharmacology
Biology and Life Sciences
Cancer therapies
Carcinoma, Pancreatic Ductal - metabolism
Carcinoma, Pancreatic Ductal - pathology
Care and treatment
Caspase
Cell adhesion & migration
Cell Line, Tumor
Cell lines
Cell Survival - drug effects
Chemotherapy
Deoxyribonucleic acid
DNA
DNA (Cytosine-5-)-Methyltransferase 1 - metabolism
DNA methylation
DNA methyltransferase
DNMT1 protein
Drug resistance
Epigenesis, Genetic - drug effects
Epigenetic inheritance
Epigenetics
Gene expression
Humans
Immunotherapy
Irinotecan
Irinotecan - pharmacology
Medical research
Medicine and Health Sciences
Metastasis
Modulators
Oncology
Pancreas
Pancreas - drug effects
Pancreas - metabolism
Pancreas - pathology
Pancreatic cancer
Pancreatic Neoplasms - metabolism
Pancreatic Neoplasms - pathology
Patient outcomes
Research and Analysis Methods
Topoisomerase I Inhibitors - pharmacology
Tumors
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Pancreatic ductal adenocarcinoma (PDAC) is expected to be the second leading cause of cancer mortality by 2030. PDAC remains resistant to the majority of systemic chemotherapies. In this paper, we explore if epigenetic sensitization can improve chemotherapy response in PDAC. Multiple PDAC cell lines were tested with serial concentrations of the epigenetic modulators 5-azacitidine (Aza) and guadecitabine (SGI-110). Guadecitabine was effective at inhibiting the expression of DNA Methyltransferase 1 (DNMT1) and in decreasing cell viability at nanomolar concentrations. We also report that guadecitabine has increased efficacy following a delay period or as we reference, a 'rest period'. Sensitization with guadecitabine improved response to the chemotherapeutic agent-Irinotecan- as measured by decreased cell viability and accompanied by an increase in caspase activity. Additional studies are needed to understand the mechanism of action.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0199130