Red and brown algae have been shown to produce a variety of compounds with chemotherapeutic potential. A recent report described the isolation of a range of novel polyhalogenated
monoterpene compounds from the red algae Plocamium corallorhiza and Plocamium cornutum collected off the coast of South Africa, together with the previously described tetraprenylquinone,
sargaquinoic acid (SQA), from the brown algae Sargassum heterophyllum. In our study, the algal compounds were screened for anti-proliferative activity against metastatic MDA-MB-231
breast cancer cells revealing that a number of compounds displayed anti-
cancer activity with IC(50) values in the micromolar range. A subset of the compounds was tested for differential toxicity in the MCF-7/MCF12A system and five of these, including
sargaquinoic acid, were found to be at least three times more toxic to the
breast cancer than the non-malignant cell line. SQA was further analysed in terms of its mechanism of cytotoxicity in MDA-MB-231 cells. The ability to initiate apoptosis was distinguished from the induction of an inflammatory necrotic response via flow cytometry with
propidium iodide and Hoescht staining, confocal microscopy with
Annexin V and
propidium iodide staining as well as the PARP cleavage assay. We report that SQA induced apoptosis while a polyhalogenated
monoterpene RU015 induced
necrosis in metastatic
breast cancer cells in vitro. Furthermore, we demonstrated that apoptosis induction by SQA occurs via
caspase-3, -6, -8, -9 and -13 and was associated with down-regulation of Bcl-2. In addition, cell cycle analyses revealed that the compound causes G(1) arrest in MDA-MB-231 cells.