3EZ, 20Ac-ingenol-induced apoptosis in chemoresistant cancers with cyclin D1 accumulation

Shohei Miyata, Tomonori Nakamura, Susumu Kitanaka

Research output: Contribution to journalArticlepeer-review

Abstract

Background/Aim: The topoisomerase 1 catalytic inhibitor 3EZ, 20Ac-ingenol specifically induces apoptosis through the activation of ATR and the up-regulation of PTEN by enhancing the DNA damage response (DDR) in human B lymphoma (BALL-1) cells. The accumulation of cyclin D1 in cancer is known to be related to chemoresistance to DNA damage agents and nuclei of BALL-1 cells exhibit high levels of cyclin D1. However, 3EZ, 20Ac-ingenol effectively induced apoptosis of BALL-1 cells. Materials and Methods: Cell growth, protein levels, and apoptosis were determined by an MTT assay, immunoblotting and DNA fragmentation assay, respectively. Results: 3EZ, 20Ac-ingenol strongly induced inhibition of cell proliferation and apoptosis in Jeko-1 and Panc-1 cell lines through the activation of tumor suppressor proteins and caspase 3. Conclusion: 3EZ, 20Ac-ingenol-induced apoptosis might occur in cells with cyclin D1 accumulation through enhancing DDR, regardless of the cancer cell type.

Original languageEnglish
Pages (from-to)6237-6246
Number of pages10
JournalAnticancer research
Volume40
Issue number11
DOIs
Publication statusPublished - 2020 Nov

Keywords

  • ATR
  • Akt
  • Catalytic topo I inhibitor
  • Cyclin D1 accumulation
  • GSK-3β
  • PTEN

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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