Background: The cancer stem cell (CSC) theory proposes that tumours arise from and are sustained by a\r\nsubpopulation of cells with both cancer and stem cell properties. One of the key hallmarks of CSCs is the ability to\r\ngrow anchorage-independently under serum-free culture conditions resulting in the formation of tumourspheres.\r\nIt has further been reported that these cells are resistant to traditional chemotherapeutic agents.\r\nMethods: In this study, the tumoursphere assay was validated in MCF-7 cells and used to screen novel marine algal\r\ncompounds for potential anti-cancer stem cell (CSC) activity in vitro.\r\nResults: MCF-7 breast cancer cells were observed to generate tumourspheres or mammospheres after 3-5 days\r\ngrowth in anchorage-independent conditions and an apparent enrichment in potential CSCs was observed by an\r\nincrease in the proportion of CD44high/CD24low marker-bearing cells and Oct4 expression compared to those in the\r\nbulk population grown in regular adherent conditions. Using this assay, a set of algal metabolites was screened for\r\nthe ability to inhibit mammosphere development as a measure of potential anti-CSC activity. We report that the\r\npolyhalogenated monoterpene stereoisomers RU017 and RU018 isolated from the red alga Plocamium cornutum,\r\nboth of which displayed no cytotoxicity against either adherent MCF-7 breast cancer or MCF-12A non-transformed\r\nbreast epithelial cells, were able to prevent MCF-7 mammosphere formation in vitro. On the other hand, neither the\r\nbrown algal carotenoid fucoxanthin nor the chemotherapeutic paclitaxel, both of which were toxic to adherent\r\nMCF-7 and MCF-12A cells, were able to inhibit mammosphere formation. In fact, pre-treatment with paclitaxel\r\nappeared to enhance mammosphere formation and development, a finding which is consistent with the reported\r\nresistance of CSCs to traditional chemotherapeutic agents.\r\nConclusion: Due to the proposed clinical significance of CSC in terms of tumour initiation and metastasis,\r\nthe identification of agents able to inhibit this subpopulation has clinical significance.
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