Assessment of potential anti-cancer stem cell activity of marine algal compounds using an in vitro mammosphere assay

Cancer Cell International

Adrienne L Edkins²  Gregory L Blatch¹  Denzil R Beukes³  Maynard T Chiwakata³  Mugdha G Sukhthankar²  Jason N Sterrenberg²  Jo-Anne de la Mare² 

[1] College of Health and Biomedicine, Victoria University, Melbourne, Australia;The Biomedical Biotechnology Research Unit (BioBRU), Department of Biochemistry, Microbiology and Biotechnology, Rhodes University, P. O. Box 94, Grahamstown, 6140, South Africa;Division of Pharmaceutical Chemistry, Faculty of Pharmacy, Rhodes University, Grahamstown, South Africa

关键词: Halogenated monoterpenes;    Cancer stem cells;    Mammosphere assay;   

Others  :  793941
DOI  :  10.1186/1475-2867-13-39

 received in 2012-11-07, accepted in 2013-04-23,  发布年份 2013

【 摘 要 】

Background

The cancer stem cell (CSC) theory proposes that tumours arise from and are sustained by a subpopulation of cells with both cancer and stem cell properties. One of the key hallmarks of CSCs is the ability to grow anchorage-independently under serum-free culture conditions resulting in the formation of tumourspheres. It has further been reported that these cells are resistant to traditional chemotherapeutic agents.

Methods

In this study, the tumoursphere assay was validated in MCF-7 cells and used to screen novel marine algal compounds for potential anti-cancer stem cell (CSC) activity in vitro.

Results

MCF-7 breast cancer cells were observed to generate tumourspheres or mammospheres after 3-5 days growth in anchorage-independent conditions and an apparent enrichment in potential CSCs was observed by an increase in the proportion of CD44^high/CD24^low marker-bearing cells and Oct4 expression compared to those in the bulk population grown in regular adherent conditions. Using this assay, a set of algal metabolites was screened for the ability to inhibit mammosphere development as a measure of potential anti-CSC activity. We report that the polyhalogenated monoterpene stereoisomers RU017 and RU018 isolated from the red alga Plocamium cornutum, both of which displayed no cytotoxicity against either adherent MCF-7 breast cancer or MCF-12A non-transformed breast epithelial cells, were able to prevent MCF-7 mammosphere formation in vitro. On the other hand, neither the brown algal carotenoid fucoxanthin nor the chemotherapeutic paclitaxel, both of which were toxic to adherent MCF-7 and MCF-12A cells, were able to inhibit mammosphere formation. In fact, pre-treatment with paclitaxel appeared to enhance mammosphere formation and development, a finding which is consistent with the reported resistance of CSCs to traditional chemotherapeutic agents.

Conclusion

Due to the proposed clinical significance of CSC in terms of tumour initiation and metastasis, the identification of agents able to inhibit this subpopulation has clinical significance.

【 授权许可】

   
2013 de la Mare et al.; licensee BioMed Central Ltd.

【 图 表 】

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