Journal article
Identification of a thalidomide derivative that selectively targets tumorigenic liver progenitor cells and comparing its effects with lenalidomide and sorafenib
European Journal of Medicinal Chemistry, Vol.120, pp.275-283
2016
Abstract
Background & aims
The availability of non-tumorigenic and tumorigenic liver progenitor cell (LPC) lines affords a method to screen putative anti-liver cancer agents to identify those that are selectively effective. To prove this principle we tested thalidomide and a range of its derivatives and compared them to lenalidomide and sorafenib, to assess their growth-inhibitory effects.
Methods
Cell growth, the mitotic and apoptotic index of cell cultures were measured using the Cellavista instrument (SynenTec) using commercially available reagents.
Results
Neither lenalidomide nor thalidomide (100 μM) affected tumorigenic LPCs but killed their non-tumorigenic counterparts. Sorafenib arrested growth in both cell types. All but two derivatives of thalidomide were ineffective; of the two effective derivatives, one (thalidomide C1) specifically affected the tumorigenic cell line (10 μM). Mitotic and apoptotic analyses revealed that thalidomide C1 induced apoptotic cell death and not mitotic arrest.
Conclusions
This study shows that screens incorporating non-tumorigenic and tumorigenic liver cell lines are a sound approach to identify agents that are effective and selective. A high throughput instrument such as the Cellavista affords robust and reproducible objective measurements with a large number of replicates that are reliable. These experiments show that neither lenalidomide nor thalidomide are potentially useful for anti-liver cancer therapy as they kill non-tumorigenic liver cells and not their tumorigenic counterparts. Sorafenib in contrast, is highly effective, but not selective. One tested thalidomide derivative has potential as an anti-tumor drug since it induced growth arrest; and importantly, it selectively induced apoptotic cell death only in tumorigenic liver progenitor cells.
Details
- Title
- Identification of a thalidomide derivative that selectively targets tumorigenic liver progenitor cells and comparing its effects with lenalidomide and sorafenib
- Authors/Creators
- K. Woo (Author/Creator) - Harry Perkins Institute of Medical ResearchS.G. Stewart (Author/Creator) - The University of Western AustraliaG.S. Kong (Author/Creator) - The University of Western AustraliaM.L. Finch-Edmondson (Author/Creator) - The University of Western AustraliaB.J. Dwyer (Author/Creator) - Harry Perkins Institute of Medical ResearchS.Y. Yeung (Author/Creator) - The University of Western AustraliaL.J. Abraham (Author/Creator) - The University of Western AustraliaS.S. Kampmann (Author/Creator) - The University of Western AustraliaL.A. Diepeveen (Author/Creator) - Harry Perkins Institute of Medical ResearchA.M. Passman (Author/Creator) - The University of Western AustraliaC.L. Elsegood (Author/Creator) - Curtin UniversityJ.E.E. Tirnitz-Parker (Author/Creator) - Curtin UniversityB.A. Callus (Author/Creator) - The University of Western AustraliaJ.K. Olynyk (Author/Creator) - Fiona Stanley HospitalG.C.T. Yeoh (Author/Creator) - School of Molecular Sciences
- Publication Details
- European Journal of Medicinal Chemistry, Vol.120, pp.275-283
- Publisher
- Elsevier Masson SAS
- Identifiers
- 991005541167807891
- Copyright
- © 2016 Elsevier Masson SAS.
- Murdoch Affiliation
- School of Veterinary and Life Sciences
- Language
- English
- Resource Type
- Journal article
UN Sustainable Development Goals (SDGs)
This output has contributed to the advancement of the following goals:
Source: InCites
Metrics
214 File views/ downloads
45 Record Views
InCites Highlights
These are selected metrics from InCites Benchmarking & Analytics tool, related to this output
- Collaboration types
- Domestic collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.130 Lymphomas
- 1.130.617 Multiple Myeloma
- Web Of Science research areas
- Chemistry, Medicinal
- ESI research areas
- Chemistry