title: Quinones and halogenated monoterpenes of algal origin show anti-proliferative effects against breast cancer cells in vitro.
abstract: 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.
authors.affiliation: The Biomedical Biotechnology Research Unit (BioBRU), Department of Biochemistry, Microbiology and Biotechnology, Rhodes University, P. O. Box 94, Grahamstown, 6140, South Africa.
authors.forename: Jo-Anne
authors.initials: JA
authors.lastname: de la Mare
authors.forename: Jessica C
authors.initials: JC
authors.lastname: Lawson
authors.forename: Maynard T
authors.initials: MT
authors.lastname: Chiwakata
authors.forename: Denzil R
authors.initials: DR
authors.lastname: Beukes
authors.forename: Adrienne L
authors.initials: AL
authors.lastname: Edkins
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Blatch
mesh_terms: D000475:Alkenes / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D016227:Benzoquinones / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D006801:Humans; D039821:Monoterpenes / Q000494:pharmacology*; D044725:Plocamium; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D044647:Sargassum
chemical_list: D000475:Alkenes; D000972:Antineoplastic Agents, Phytogenic; D016227:Benzoquinones; D039821:Monoterpenes; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; C477718:sargaquinoic acid; D020169:Caspases