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Updated: May 27, 2026
13:20
Detection of Mitochondria Membrane Potential to Study CLIC4 Knockdown-induced HN4 Cell Apoptosis In Vitro
Published on: July 17, 2018
WIN55,212-2 induces cytoplasmic vacuolation in apoptosis-resistant MCL cells
A M Wasik1, S Almestrand, X Wang
1Division of Pathology, Department of Laboratory Medicine, F46, Karolinska Institutet, Karolinska University Hospital, Huddinge, SE 141 86 Stockholm, Sweden. agata.wasik@ki.se
Cell Death & Disease
|November 4, 2011
Summary
Cannabinoid receptor agonists trigger a novel cell death pathway in some mantle cell lymphomas (MCLs). This process involves cytoplasmic vacuole formation from the endoplasmic reticulum, distinct from apoptosis.
Area of Science:
- Cancer Biology
- Cell Death Mechanisms
- Pharmacology
Background:
- Cannabinoid receptors 1 (CB1) and 2 (CB2) are overexpressed in human malignancies, including mantle cell lymphoma (MCL).
- CB1/CB2 agonists typically induce apoptosis in MCLs via ceramide synthesis and caspase-3 activation.
Purpose of the Study:
- To investigate the cellular response to cannabinoid treatment in MCLs that do not undergo apoptosis.
- To characterize the mechanism of cell death induced by cannabinoids in specific MCL subtypes.
Main Methods:
- Treatment of primary MCL cells and the Granta519 MCL cell line with cannabinoid agonists.
- Assessment of cell viability using metabolic activity assays.
- Analysis of apoptotic markers (caspase-3, plasma membrane integrity).
- Microscopy (TEM, immunofluorescence) to identify vacuole origin and cellular changes.
- Investigation of autophagy markers (LC3 II, p62) and response to chloroquine.
Main Results:
- Cannabinoid treatment reduced metabolic activity but did not induce caspase-3 activation or plasma membrane damage in some MCLs.
- Formation of cycloheximide-sensitive cytoplasmic vacuoles of endoplasmic reticulum origin was observed.
- The process was distinguished from classical autophagy, as lysosomal degradation was not involved.
- Cell death features resembled paraptosis, a programmed cell death pathway not previously linked to cannabinoids.
Conclusions:
- Cannabinoids can induce a non-apoptotic programmed cell death, termed paraptosis-like cell death, in certain MCLs.
- This pathway involves ER-derived cytoplasmic vacuolation and is independent of lysosomal degradation.
- Identifies a novel mechanism of cannabinoid-induced cell death in cancer, potentially offering new therapeutic strategies.
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