Abstract
BackgroundThe 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.MethodsIn 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.ResultsMCF-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 CD44high/CD24low 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.ConclusionDue 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.
Highlights
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
Paclitaxel and fucoxanthin, but not the monoterpenes RU017 and RU018, are toxic towards breast cancer and non-transformed breast epithelial cells in vitro The differential toxicity of the algal polyhalogenated monoterpenes RU017 and RU018, as well as the carotenoid fucoxanthin (FXN) and the chemotherapeutic paclitaxel (Ptx), against breast cancer and non-transformed breast epithelial cells was assessed by MTT assay
For the halogenated monoterpenes RU017 and RU018, neither of the compounds was toxic to MCF-7 or MDA-MB-231 breast cancer or MCF-12A non-transformed breast epithelial cell lines, even at a concentration of 300 μM (Table 1)
Summary
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. The cancer stem cell theory challenges the traditional monoclonal models of cancer development and has revolutionized the way we think about the origin and progression of cancers [1,2] This theory states that tumours consist of a heterogenous population of cells. Breast cancer stem-like cells have been isolated based on their functional characteristics; in particular their ability to grow anchorageindependently in serum-free conditions [7,9]. In these culture conditions non-stem cancer cells undergo anoikis, a programmed cell death associated with loss of adhesion, selecting for the CSC-like subpopulation [10,11]. These CSC-like cells form tumourspheres or mammospheres in suspension in vitro, have been shown to be capable of in vivo tumour formation at limiting cell dilutions and express high levels of stem cell markers such as Oct4 [7,9,12]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
