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Updated: Dec 3, 2025

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics
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3EZ, 20Ac-ingenol-induced Apoptosis in Chemoresistant Cancers With Cyclin D1 Accumulation

Shohei Miyata1, Tomonori Nakamura2, Susumu Kitanaka3

  • 1Department of Chemistry, College of Humanities and Sciences, Nihon University, Tokyo, Japan s.miya0024@mbr.nifty.com.

Anticancer Research
|October 28, 2020
PubMed
Abstract

Insights

The novel compound 3EZ, 20Ac-ingenol effectively induces apoptosis in cancer cells by enhancing the DNA damage response (DDR). This topoisomerase 1 inhibitor shows promise against chemoresistant cells, including those with cyclin D1 accumulation.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Cyclin D1 accumulation is linked to chemoresistance in cancer cells treated with DNA damage agents.
  • Human B lymphoma (BALL-1) cells exhibit high nuclear cyclin D1 levels.
  • 3EZ, 20Ac-ingenol is a topoisomerase 1 catalytic inhibitor.

Purpose of the Study:

  • To investigate the mechanism of apoptosis induction by 3EZ, 20Ac-ingenol in cancer cells.
  • To determine the role of DNA damage response (DDR) in 3EZ, 20Ac-ingenol-mediated apoptosis.
  • To assess the efficacy of 3EZ, 20Ac-ingenol in cells with high cyclin D1 levels.

Main Methods:

  • Cell proliferation was assessed using MTT assays.
  • Protein levels were analyzed via immunoblotting.
  • Apoptosis was quantified using DNA fragmentation assays.

Main Results:

  • 3EZ, 20Ac-ingenol significantly inhibited cell proliferation and induced apoptosis in Jeko-1 and Panc-1 cell lines.
  • The compound activated tumor suppressor proteins and caspase 3.
  • Apoptosis was mediated through enhanced DNA damage response (DDR), involving ATR activation and PTEN up-regulation.

Conclusions:

  • 3EZ, 20Ac-ingenol effectively induces apoptosis in cancer cells with cyclin D1 accumulation.
  • The mechanism involves enhancing the DNA damage response (DDR).
  • This effect appears independent of cancer cell type, suggesting broad applicability.
Keywords:
ATRAktCatalytic topo I inhibitorGSK-3βPTENcyclin D1 accumulation

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