The sesquiterpene lactone dehydroleucodine triggers senescence and apoptosis in association with accumulation of DNA damage markers.

PLoS One

Laboratory of Cell Cycle and Cytoskeleton, Instituto de Histología y Embriología Dr. M. H. Burgos (IHEM), Facultad de Ciencias Medicas, Universidad Nacional de Cuyo, Mendoza, Argentina.

Published: July 2013


Category Ranking

98%

Total Visits

921

Avg Visit Duration

2 minutes

Citations

20

Article Abstract

Sesquiterpene lactones (SLs) are plant-derived compounds that display anti-cancer effects. Some SLs derivatives have a marked killing effect on cancer cells and have therefore reached clinical trials. Little is known regarding the mechanism of action of SLs. We studied the responses of human cancer cells exposed to various concentrations of dehydroleucodine (DhL), a SL of the guaianolide group isolated and purified from Artemisia douglasiana (Besser), a medicinal herb that is commonly used in Argentina. We demonstrate for the first time that treatment of cancer cells with DhL, promotes the accumulation of DNA damage markers such as phosphorylation of ATM and focal organization of γH2AX and 53BP1. This accumulation triggers cell senescence or apoptosis depending on the concentration of the DhL delivered to cells. Transient DhL treatment also induces marked accumulation of senescent cells. Our findings help elucidate the mechanism whereby DhL triggers cell cycle arrest and cell death and provide a basis for further exploration of the effects of DhL in in vivo cancer treatment models.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3544853PMC
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0053168PLOS

Publication Analysis

Top Keywords

cancer cells
12
senescence apoptosis
8
accumulation dna
8
dna damage
8
damage markers
8
triggers cell
8
dhl
6
cells
5
sesquiterpene lactone
4
lactone dehydroleucodine
4

Similar Publications

Systemic Delivery of an mRNA-Encoding, Tumor-Activated Interleukin-12 Lock to Eliminate Tumors and Avoid Immune-Related Adverse Events.

Nano Lett

September 2025

Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha 410082, China.

Interleukin-12 (IL-12) is a robust proinflammatory cytokine that activates immune cells, such as T cells and natural killer cells, to induce antitumor immunity. However, the clinical application of recombinant IL-12 has been limited by systemic immune-related adverse events (irAEs) and rapid degradation. To address these challenges, we employed mRNA technology to encode a tumor-activated IL-12 "lock" fusion protein that offers both therapeutic efficacy and systemic safety.

View Article and Find Full Text PDF

Roles of Extracellular Superoxide Dismutase in Regulating Cell Migration and Vesicle Trafficking in Dictyostelium and Mammalian Cells.

Dev Growth Differ

September 2025

Department of Biological Sciences, College of Arts, Sciences, and Education, Florida International University, Miami, Florida, USA.

Superoxide dismutases (SODs) are key regulators of reactive oxygen species (ROS) and redox balance. Although intracellular SODs have been extensively studied, growing attention has been directed toward understanding the roles of extracellular SODs in both Dictyostelium and mammalian systems. In Dictyostelium discoideum, SodC is a glycosylphosphatidylinositol (GPI)-anchored enzyme that modulates extracellular superoxide to regulate Ras, PI3K signaling, and cytoskeletal remodeling during directional cell migration.

View Article and Find Full Text PDF

Background And Aims: Liver metastasis significantly contributes to poor survival in patients with colorectal cancer (CRC), posing therapeutic challenges due to limited understanding of its mechanisms. We aimed to identify a potential target critical for CRC liver metastasis.

Methods: We analyzed the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) databases and identified EphrinA3 (EFNA3) as a potential clinically relevant target.

View Article and Find Full Text PDF

NSUN6 Promotes Gastric Cancer Progression by Stabilizing CEBPZ mRNA in a mC-Dependent Manner.

Appl Biochem Biotechnol

September 2025

Operating Room, Shanghai Tianyou Hospital, No.528, Zhennan Road, Putuo District, Shanghai, 200331, China.

Gastric cancer (GC) is a malignant tumor originating from the epithelial cells of the gastric mucosa. The 5-methylcytosine (mC) modification refers to the addition of a methyl group to the fifth carbon atom of cytosine in RNA molecules. This study aimed to investigate the role of NOL1/NOP2/SUN domain (NSUN)6 in GC and its underlying molecular mechanisms.

View Article and Find Full Text PDF