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Updated: Mar 22, 2026

Cell Death Associated with Abnormal Mitosis Observed by Confocal Imaging in Live Cancer Cells
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Novel Benzo[a]quinolizidine Analogs Induce Cancer Cell Death through Paraptosis and Apoptosis

Hongbo Zheng1, Yiwen Dong1, Lin Li1

  • 1Department of Natural Products Chemistry, Key Laboratory of Chemical Biology of Ministry of Education, School of Pharmaceutical Sciences, ‡Department of Biochemistry and Molecular Biology, School of Medicine, and §National Glycoengineering Research Center, Shandong University , No.44 Western Wenhua Road, Jinan 17923, China.

Journal of Medicinal Chemistry
|April 15, 2016
PubMed

Insights

Novel benzo[a]quinolizidine derivatives induce paraptosis, a nonapoptotic cell death, offering a promising alternative for chemotherapy-resistant cancers. Compound 22b shows potent antiproliferative activity by triggering cytoplasmic vacuolation and ER stress.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Pharmacology

Background:

  • Paraptosis is a nonapoptotic cell death pathway marked by cytoplasmic vacuolation, distinct from apoptosis.
  • Paraptosis induction presents advantages for treating chemotherapy-resistant tumors.
  • Natural alkaloids can induce paraptotic cell death, suggesting potential therapeutic applications.

Purpose of the Study:

  • To synthesize novel benzo[a]quinolizidine derivatives.
  • To evaluate their antiproliferative activity and capacity to induce cytoplasmic vacuolation.
  • To explore paraptosis as a therapeutic strategy for cancer.

Main Methods:

  • Synthesis of benzo[a]quinolizidine derivatives.
  • In vitro and in vivo antiproliferative assays.
  • Analysis of cytoplasmic vacuolation and cell death pathways.
  • Investigation of endoplasmic reticulum (ER) stress and LC3B expression.

Main Results:

  • Compound 22b demonstrated potent inhibition of cancer cell proliferation.
  • 22b induced paraptosis-like cell death and caspase-dependent apoptosis.
  • 22b-mediated vacuolation was linked to persistent ER stress and LC3B upregulation.
  • Benzo[a]quinolizidine derivatives show promise as anticancer agents.

Conclusions:

  • Novel benzo[a]quinolizidine derivatives can effectively induce paraptosis.
  • Compound 22b is a potent agent against cancer cell proliferation.
  • Paraptosis induction via ER stress and LC3B modulation is a viable anticancer strategy.

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