Pancreas. 2012 Oct;41(7):1039-47.

Selective induction of apoptosis and autophagy through treatment with dandelion root extract in human pancreatic cancer cells.

Ovadje P, Chochkeh M, Akbari-Asl P, Hamm C, Pandey S.

Department of Chemistry and Biochemistry, University of Windsor, Windsor, Ontario, Canada.

 

Abstract

OBJECTIVES: Pancreatic cancer has a 100% mortality rate; the aim of this study is to evaluate the efficacy of dandelion root extract (DRE) in inducing apoptosis and autophagy in aggressive and resistant pancreatic cancer cells.

METHODS: The effect of DRE was evaluated using WST-1 (4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate) assay. Apoptotic cell death was confirmed by nuclear condensation by Hoechst staining and externalization of phosphatidylserine to the outer leaflet of the plasma membrane by Annexin-V binding assay. Loss of mitochondrial membrane potential was observed using the JC-1 (5,5′,6, 6′-tetrachloro-1,1′,3,3′ tetraethylbenzimidazolylcarbocyanine iodide) dye. The induction of autophagy was detected using a monodansylcadaverine assay and this was confirmed by immunofluorescence for light chain 3-II.

RESULTS: BxPC-3 and PANC-1 pancreatic cells were sensitive to aqueous DRE. This extract induces selective apoptosis in a dose- and time-dependent manner. Dandelion root extract caused the collapse of the mitochondrial membrane potential, leading to prodeath autophagy. Normal human fibroblasts were resistant at similar doses.

CONCLUSIONS: We demonstrate that DRE has the potential to induce apoptosis and autophagy in human pancreatic cancer cells with no significant effect on noncancerous cells. This will provide a basis on which further research in cancer treatment through DRE can be executed.

PMID: 22647733

 

SUPPLEMENT:

There is increasing evidence for the role of Natural Health Products (NHPs) in the treatment of various diseases. More importantly, dandelion root extract (DRE) has been marketed for its various activities in the gastrointestinal system and its potential activity with anti-inflammatory and antioxidant properties. In this study, we show that DRE was efficient in inducing apoptosis and pro-death autophagy in pancreatic cancer cells, surprisingly with no associated toxicities to non-cancerous cells. The mechanism of cell death induction in pancreatic cancer cells is not fully understood; however the results from this study show that DRE targets the extrinsic pathway of apoptosis to rapidly induce apoptosis. The complexity of this extract leads us to believe that the presence of multiple components may target different pathways for the induction of cell death. Indeed we observed direct targeting of isolated mitochondria and mitochondrial membrane destabilization, following DRE treatment. This is indicated in the flowchart of the mechanism of DRE’s activity in pancreatic cancer cells (Figure 1). At this stage, we are in the process of identifying the bioactive component(s) in DRE to better understand its mechanism of action. Recent data suggests the beneficial effect of combining multiple components, which yields better efficacy than single component treatment. DRE in combination with embelin, a small molecular weight natural compound inhibitor of XIAP, had synergistic effects, showing better efficacy at lower doses than DRE or embelin alone (Figure 2). This suggests that the complex mixture of DRE, which can be provided orally as a safe NHP, is more beneficial than isolating a single component. These findings present an exciting possibility and an alternative safer treatment for pancreatic cancer, using combination of NHPs and natural compounds.

Flowchart-for-PANCREAS-Biomedical-Frontiers Fig 1. The flowchart of the mechanism of DRE’s activity in pancreatic cancer cells.


Figures-for-PANCREAS-Biomedical-Frontiers Fig 2. Enhancement of DRE’s activity by Embelin: Human Pancreatic cancer cells (PANC-1) were treated with DRE and Embelin, alone and in combination for 24 hours. The nuclear and cellular morphology was recorded by hoechst staining and phase contrast microscopy respectively. The results indicate apoptotic morphology and condensed nuclei, follwing these treatment. A synergistic effect was observed with the combined treatment, which shows a distinct lack of live healthy cells after treatment.


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