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

Manjusha Thakar, Yue Hu, Michael Morreale, Lane Lerner, Wan Ying Lin, Rupashree Sen, Yi Cai, Enusha Karunasena, Maya Thakar, Soren Saggi, Harold Keer, Nita Ahuja

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article numbere0199130
JournalPLoS One
Volume13
Issue number6
DOIs
StatePublished - Jun 1 2018

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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    Thakar, M., Hu, Y., Morreale, M., Lerner, L., Lin, W. Y., Sen, R., Cai, Y., Karunasena, E., Thakar, M., Saggi, S., Keer, H., & Ahuja, N. (2018). A novel epigenetic modulating agent sensitizes pancreatic cells to a chemotherapy agent. PLoS One, 13(6), [e0199130]. https://doi.org/10.1371/journal.pone.0199130