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Erschienen in: Investigational New Drugs 6/2012

01.12.2012 | PRECLINICAL STUDIES

Quinones and halogenated monoterpenes of algal origin show anti-proliferative effects against breast cancer cells in vitro

verfasst von: Jo-Anne de la Mare, Jessica C. Lawson, Maynard T. Chiwakata, Denzil R. Beukes, Adrienne L. Edkins, Gregory L. Blatch

Erschienen in: Investigational New Drugs | Ausgabe 6/2012

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Summary

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 IC50 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 G1 arrest in MDA-MB-231 cells.
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Literatur
1.
Zurück zum Zitat World Health Statistics (2008) Part 1: ten highlights in health statistics, breast cancer: mortality and screening. World Health Organisation, Geneva, pp 21–23 World Health Statistics (2008) Part 1: ten highlights in health statistics, breast cancer: mortality and screening. World Health Organisation, Geneva, pp 21–23
2.
Zurück zum Zitat Peto R, Boreham J, Clarke M, Davies C, Beral V (2000) UK and USA breast cancer deaths down 25% in year 2000 at ages 20–69 years. Lancet 355:1822–1822PubMedCrossRef Peto R, Boreham J, Clarke M, Davies C, Beral V (2000) UK and USA breast cancer deaths down 25% in year 2000 at ages 20–69 years. Lancet 355:1822–1822PubMedCrossRef
3.
Zurück zum Zitat Howe HL, Wingo PA, Thun MJ, Ries LA, Rosenberg HM, Feigal EG, Edwards BK (2001) Annual report to the nation on the status of cancer (1973 through 1998), featuring cancers with recent increasing trends. J Natl Cancer Inst 93:824–842PubMedCrossRef Howe HL, Wingo PA, Thun MJ, Ries LA, Rosenberg HM, Feigal EG, Edwards BK (2001) Annual report to the nation on the status of cancer (1973 through 1998), featuring cancers with recent increasing trends. J Natl Cancer Inst 93:824–842PubMedCrossRef
4.
Zurück zum Zitat Zhou J, Zhang H, Gu P, Bai J, Margolick M, Zhang Y (2008) NF-κB pathway inhibitors preferentially inhibit breast cancer stem-like cells. Breast Canc Res Treat 111:419–427CrossRef Zhou J, Zhang H, Gu P, Bai J, Margolick M, Zhang Y (2008) NF-κB pathway inhibitors preferentially inhibit breast cancer stem-like cells. Breast Canc Res Treat 111:419–427CrossRef
5.
Zurück zum Zitat Jin Z, El-Deiry WS (2005) Overview of cell death signaling pathways. Canc Biol Ther 4(2):139–163CrossRef Jin Z, El-Deiry WS (2005) Overview of cell death signaling pathways. Canc Biol Ther 4(2):139–163CrossRef
6.
Zurück zum Zitat Iannolo G, Conticello C, Memeo L, De Maria R (2008) Apoptosis in normal and cancer cells. Crit Rev Oncol Hematol 66:42–51PubMedCrossRef Iannolo G, Conticello C, Memeo L, De Maria R (2008) Apoptosis in normal and cancer cells. Crit Rev Oncol Hematol 66:42–51PubMedCrossRef
7.
Zurück zum Zitat Fink SL, Cookson BT (2005) Apoptosis, pyroptosis, and necrosis: mechanistic description of dead and dying eukaryotic cells. Infect Immun 73:1907–1916PubMedCrossRef Fink SL, Cookson BT (2005) Apoptosis, pyroptosis, and necrosis: mechanistic description of dead and dying eukaryotic cells. Infect Immun 73:1907–1916PubMedCrossRef
8.
Zurück zum Zitat Klener P Jr, Andera L, Klener P, Necas E, Zivny J (2006) Cell death signalling pathways in the pathogenesis and therapy of haematologic malignancies: overview of apoptotic pathways. J Folia Biol (Praha) 52:34–44 Klener P Jr, Andera L, Klener P, Necas E, Zivny J (2006) Cell death signalling pathways in the pathogenesis and therapy of haematologic malignancies: overview of apoptotic pathways. J Folia Biol (Praha) 52:34–44
9.
Zurück zum Zitat Leist M, Jaattela M (2001) Four deaths and a funeral: from caspases to alternative mechanisms. Nat Rev Mol Cell Biol 2:589–98PubMedCrossRef Leist M, Jaattela M (2001) Four deaths and a funeral: from caspases to alternative mechanisms. Nat Rev Mol Cell Biol 2:589–98PubMedCrossRef
11.
12.
Zurück zum Zitat Kerr JF, Wyllie AH, Currie AR (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 26:239–57PubMedCrossRef Kerr JF, Wyllie AH, Currie AR (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 26:239–57PubMedCrossRef
13.
Zurück zum Zitat Debatin K-M, Krammer PH (2004) Death receptors in chemotherapy and cancer. Oncogene 23:2950–2966PubMedCrossRef Debatin K-M, Krammer PH (2004) Death receptors in chemotherapy and cancer. Oncogene 23:2950–2966PubMedCrossRef
14.
Zurück zum Zitat Boulares AH, Yakovlev AG, Ivanova V, Stoica BA, Wang G, Iyer S, Smulson M (1999) Role of poly(ADP-ribose) polymerase (PARP) cleavage in apoptosis. Caspase 3-resistant PARP mutant increases rates of apoptosis in transfected cells. J Biol Chem 274:22932–22940PubMedCrossRef Boulares AH, Yakovlev AG, Ivanova V, Stoica BA, Wang G, Iyer S, Smulson M (1999) Role of poly(ADP-ribose) polymerase (PARP) cleavage in apoptosis. Caspase 3-resistant PARP mutant increases rates of apoptosis in transfected cells. J Biol Chem 274:22932–22940PubMedCrossRef
15.
Zurück zum Zitat Carté BK (1996) Biomedical potential of marine natural products. Bioscience 46(4):271–286CrossRef Carté BK (1996) Biomedical potential of marine natural products. Bioscience 46(4):271–286CrossRef
16.
Zurück zum Zitat Jha RK, Zi-rong X (2004) Biomedical compounds from marine organisms. Mar Drugs 2:123–146CrossRef Jha RK, Zi-rong X (2004) Biomedical compounds from marine organisms. Mar Drugs 2:123–146CrossRef
17.
Zurück zum Zitat König GM, Wright AD, Franzblau SG (2000) Assessment of antimycobacterial activity of a series of mainly marine derived natural products. Planta Medica 66:337–342PubMedCrossRef König GM, Wright AD, Franzblau SG (2000) Assessment of antimycobacterial activity of a series of mainly marine derived natural products. Planta Medica 66:337–342PubMedCrossRef
18.
Zurück zum Zitat Blunt JW, Copp BR, Munro MHG, Northcote PT, Prinsep MR (2003) Marine natural products. Nat Prod Rep 20:1–48PubMedCrossRef Blunt JW, Copp BR, Munro MHG, Northcote PT, Prinsep MR (2003) Marine natural products. Nat Prod Rep 20:1–48PubMedCrossRef
19.
Zurück zum Zitat Knott MG, Mkwananzi HB, Arendse CE, Hendricks DT, Bolton JJ, Beukes DR (2005) Plocoralides A-C, polyhalogenated monoterpenes from the marine alga Plocamium corallorhiza. Phytochem 66:1108–1112CrossRef Knott MG, Mkwananzi HB, Arendse CE, Hendricks DT, Bolton JJ, Beukes DR (2005) Plocoralides A-C, polyhalogenated monoterpenes from the marine alga Plocamium corallorhiza. Phytochem 66:1108–1112CrossRef
20.
Zurück zum Zitat Fuller RW, Cardellina JH II, Kato Y, Brinen LS, Clardy J, Snader KM, Boyd MR (1992) A pentahalogenated monoterpene from the red alga Portieria hornemannii produces a novel cytotoxicity profile against a diverse panel of human tumor cell lines. J Med Chem 35:3007–3011PubMedCrossRef Fuller RW, Cardellina JH II, Kato Y, Brinen LS, Clardy J, Snader KM, Boyd MR (1992) A pentahalogenated monoterpene from the red alga Portieria hornemannii produces a novel cytotoxicity profile against a diverse panel of human tumor cell lines. J Med Chem 35:3007–3011PubMedCrossRef
21.
Zurück zum Zitat Mann MGA, Mkwananzi HB, Antunes EM, Whibley CE, Hendricks DT, Bolton JJ, Beukes DR (2007) Halogenated monoterpene aldehydes from the South African marine alga Plocomium corallorhiza. J Nat Prod 70:596–599PubMedCrossRef Mann MGA, Mkwananzi HB, Antunes EM, Whibley CE, Hendricks DT, Bolton JJ, Beukes DR (2007) Halogenated monoterpene aldehydes from the South African marine alga Plocomium corallorhiza. J Nat Prod 70:596–599PubMedCrossRef
22.
Zurück zum Zitat Afolayan AF, Bolton JJ, Lategan CA, Smith PJ, Beukes DR (2008) Fucoxanthin, tetraprenylated toluquinone and toluhydroquinone metabolites from Sargassum heterophyllum inhibit the in vitro growth of the malaria parasite Plasmodium falciparum. Z Naturforsch 63c:848–852 Afolayan AF, Bolton JJ, Lategan CA, Smith PJ, Beukes DR (2008) Fucoxanthin, tetraprenylated toluquinone and toluhydroquinone metabolites from Sargassum heterophyllum inhibit the in vitro growth of the malaria parasite Plasmodium falciparum. Z Naturforsch 63c:848–852
23.
Zurück zum Zitat Hur S, Lee H, Kim Y, Lee B-H, Shin J, Kim TY (2008) Sargaquinoic acid and sargachromenal, extracts of Sargassum sagamianum induce apoptosis in HaCaT cells and mice skin: Its potentiation of UVB-induced apoptosis. Eur J Pharmacol 582:1–11PubMedCrossRef Hur S, Lee H, Kim Y, Lee B-H, Shin J, Kim TY (2008) Sargaquinoic acid and sargachromenal, extracts of Sargassum sagamianum induce apoptosis in HaCaT cells and mice skin: Its potentiation of UVB-induced apoptosis. Eur J Pharmacol 582:1–11PubMedCrossRef
24.
Zurück zum Zitat Warleta F, Campos M, Allouche Y, Sanchez-Quesada C, Ruiz-Mora J, Beltran G, Gaforio JJ (2010) Squalene protects against oxidative DNA damage in MCF10A human mammary epithelial cells but not in MCF-7 and MDA-MB-231 human breast cancer cells. Food Chem Toxicol 48:1092–1100PubMedCrossRef Warleta F, Campos M, Allouche Y, Sanchez-Quesada C, Ruiz-Mora J, Beltran G, Gaforio JJ (2010) Squalene protects against oxidative DNA damage in MCF10A human mammary epithelial cells but not in MCF-7 and MDA-MB-231 human breast cancer cells. Food Chem Toxicol 48:1092–1100PubMedCrossRef
25.
Zurück zum Zitat Lipinski CA, Lombardo F, Dominy BW, Feeney PJ (2001) Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev 46:3–26PubMedCrossRef Lipinski CA, Lombardo F, Dominy BW, Feeney PJ (2001) Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev 46:3–26PubMedCrossRef
26.
Zurück zum Zitat Chiosis G (2003) Targeting chaperones in transformed systems–a focus on Hsp90 and cancer. Expert Opin Ther Targets 10:37–50CrossRef Chiosis G (2003) Targeting chaperones in transformed systems–a focus on Hsp90 and cancer. Expert Opin Ther Targets 10:37–50CrossRef
27.
Zurück zum Zitat Chaitanya GV, Babu PP (2009) Differential PARP cleavage: an indication of heterogeneous forms of cell death and involvement of multiple proteases in the infarct of focal cerebral ischemia in rat. Cell Mol Neurobiol 29:563–573PubMedCrossRef Chaitanya GV, Babu PP (2009) Differential PARP cleavage: an indication of heterogeneous forms of cell death and involvement of multiple proteases in the infarct of focal cerebral ischemia in rat. Cell Mol Neurobiol 29:563–573PubMedCrossRef
28.
Zurück zum Zitat Tzu-Hao W, Hsin-Shih W, Yung-Kwei S (2000) Paclitaxel induced cell death. Cancer 88:2619–2628CrossRef Tzu-Hao W, Hsin-Shih W, Yung-Kwei S (2000) Paclitaxel induced cell death. Cancer 88:2619–2628CrossRef
29.
Zurück zum Zitat Choi BW, Park SH, Kim ES, Shin J, Roh SS, Shin HC, Lee BH (2007) Anticholinesterase activity of plastoquinones from Sargassum sagamianum: lead compounds for Alzheimer’s disease therapy. Phytother Res 21:423–426PubMedCrossRef Choi BW, Park SH, Kim ES, Shin J, Roh SS, Shin HC, Lee BH (2007) Anticholinesterase activity of plastoquinones from Sargassum sagamianum: lead compounds for Alzheimer’s disease therapy. Phytother Res 21:423–426PubMedCrossRef
30.
Zurück zum Zitat Hosokawa M, Wanezaki S, Miyauchi K, Kurihara H, Kohno H, Kawabata J, Odashima S, Takahashi K (1999) Apoptosis-inducing effect of fucoxanthin on human leukemia cell line HL-60. Food Sci Technol Res 5(3):243–246CrossRef Hosokawa M, Wanezaki S, Miyauchi K, Kurihara H, Kohno H, Kawabata J, Odashima S, Takahashi K (1999) Apoptosis-inducing effect of fucoxanthin on human leukemia cell line HL-60. Food Sci Technol Res 5(3):243–246CrossRef
31.
Zurück zum Zitat Carr C, Ng J, Wigmore T (2008) The side effects of chemotherapeutic agents. Cur Anaes Crit Care 19:70–79CrossRef Carr C, Ng J, Wigmore T (2008) The side effects of chemotherapeutic agents. Cur Anaes Crit Care 19:70–79CrossRef
32.
Zurück zum Zitat Dwight ES, Lawrence WD, Carl C, Nanci LW, Hangming R, Gunter D (1997) Paclitaxel-induced apoptosis in MCF-7 breast-cancer cells. Int J Cancer 70:214–220CrossRef Dwight ES, Lawrence WD, Carl C, Nanci LW, Hangming R, Gunter D (1997) Paclitaxel-induced apoptosis in MCF-7 breast-cancer cells. Int J Cancer 70:214–220CrossRef
33.
Zurück zum Zitat Bachur NR, Gordon SL, Gee MV (1978) A general mechanism for microsomal activation of quinone anticancer agents to free radicals. Cancer Res 38:1745–1750PubMed Bachur NR, Gordon SL, Gee MV (1978) A general mechanism for microsomal activation of quinone anticancer agents to free radicals. Cancer Res 38:1745–1750PubMed
34.
Zurück zum Zitat Hoyt MT, Palchaudhuri R, Hergenrother PJ (2011) Cribrostatin 6 induces death in cancer cells through a reactive oxygen species (ROS)-mediated mechanism. Investig New Drugs 29:562–573CrossRef Hoyt MT, Palchaudhuri R, Hergenrother PJ (2011) Cribrostatin 6 induces death in cancer cells through a reactive oxygen species (ROS)-mediated mechanism. Investig New Drugs 29:562–573CrossRef
35.
Zurück zum Zitat Bertram S (2000) The molecular biology of cancer. Mol Asp Med 21:167–223CrossRef Bertram S (2000) The molecular biology of cancer. Mol Asp Med 21:167–223CrossRef
36.
Zurück zum Zitat Johnstone RW, Ruefli AA, Lowe SW (2002) Apoptosis: a link between cancer genetics and chemotherapy. Cell 108:153–164PubMedCrossRef Johnstone RW, Ruefli AA, Lowe SW (2002) Apoptosis: a link between cancer genetics and chemotherapy. Cell 108:153–164PubMedCrossRef
37.
Zurück zum Zitat Shao Y, Gao Z, Marks PA, Jiang X (2004) Apoptotic and autophagic cell death induced by histone deacetylase inhibitors. Proc Natl Acad Sci USA 101:18030–18035PubMedCrossRef Shao Y, Gao Z, Marks PA, Jiang X (2004) Apoptotic and autophagic cell death induced by histone deacetylase inhibitors. Proc Natl Acad Sci USA 101:18030–18035PubMedCrossRef
38.
Zurück zum Zitat Kamei Y, Tsang CK (2003) Sargaquinoic acid promotes neurite outgrowth via protein kinase A and MAP kinases-mediated signaling pathways in PC12D cells. Int J Dev Neurosci 21:255–262PubMedCrossRef Kamei Y, Tsang CK (2003) Sargaquinoic acid promotes neurite outgrowth via protein kinase A and MAP kinases-mediated signaling pathways in PC12D cells. Int J Dev Neurosci 21:255–262PubMedCrossRef
39.
Zurück zum Zitat Dive C, Gregory CD, Phipps DJ, Evans DL, Milner AE, Wyllie AH (1992) Analysis and discrimination of necrosis and apoptosis (programmed cell death) by multiparameter flow cytometry. Biochim Biophys Acta 1133:275–285PubMedCrossRef Dive C, Gregory CD, Phipps DJ, Evans DL, Milner AE, Wyllie AH (1992) Analysis and discrimination of necrosis and apoptosis (programmed cell death) by multiparameter flow cytometry. Biochim Biophys Acta 1133:275–285PubMedCrossRef
40.
Zurück zum Zitat Soldani C, Scovassi AI (2002) Poly(ADP-ribose) polymerase-1 cleavage during apoptosis: an update. Apoptosis 7:321–328PubMedCrossRef Soldani C, Scovassi AI (2002) Poly(ADP-ribose) polymerase-1 cleavage during apoptosis: an update. Apoptosis 7:321–328PubMedCrossRef
41.
Zurück zum Zitat Jacobson MD, Raff MC (1994) Programmed cell death and Bcl-2 protection in very low oxygen. Nature 374:814–816CrossRef Jacobson MD, Raff MC (1994) Programmed cell death and Bcl-2 protection in very low oxygen. Nature 374:814–816CrossRef
42.
Zurück zum Zitat de Ines C, Argandona VH, Rovirosa J, San-Martin A, Diaz-Marrero AR, Cueto M, Gonzalez-Coloma A (2004) Cytotoxic activity of halogenated monoterpenes from Plocamium cartilagineum. Z Naturforsch 59:339–344 de Ines C, Argandona VH, Rovirosa J, San-Martin A, Diaz-Marrero AR, Cueto M, Gonzalez-Coloma A (2004) Cytotoxic activity of halogenated monoterpenes from Plocamium cartilagineum. Z Naturforsch 59:339–344
Metadaten
Titel
Quinones and halogenated monoterpenes of algal origin show anti-proliferative effects against breast cancer cells in vitro
verfasst von
Jo-Anne de la Mare
Jessica C. Lawson
Maynard T. Chiwakata
Denzil R. Beukes
Adrienne L. Edkins
Gregory L. Blatch
Publikationsdatum
01.12.2012
Verlag
Springer US
Erschienen in
Investigational New Drugs / Ausgabe 6/2012
Print ISSN: 0167-6997
Elektronische ISSN: 1573-0646
DOI
https://doi.org/10.1007/s10637-011-9788-0

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