title: Induction of G1-phase cell cycle arrest and apoptosis pathway in MDA-MB-231 human breast cancer cells by sulfated polysaccharide extracted from Laurencia papillosa.
abstract: BACKGROUND
  Marine algae consumption is linked to law cancer incidences in countries that traditionally consume marine products. Hence, Phytochemicals are considered as potential chemo-preventive and chemotherapeutic agents against cancer. We investigated the effects of the algal sulfated polysaccharide extract (ASPE) from the red marine alga L. papillosa on MDA-MB-231 human breast cancer cell line.
  
  
  METHODS
  Flow cytometry analysis was performed to study the cell viability, cell cycle arrest and apoptosis. Changes in the expression of certain genes associated with cell cycle regulation was conducted by PCR real time analyses. Further investigations on apoptotic molecules was performed by ROS measurement and protein profiling.
  
  
  RESULTS
  ASPE at low doses (10 µg/ml), inhibited cell proliferation, and arrested proliferating MDA-MB-231 cells at G1-phase. However, higher doses (50 µg/ml), triggered apoptosis in those cells. The low dose of ASPE also caused up-regulation of Cip1/p21 and Kip1/p27 and down-regulation of cyclins D1, D2, and E1 transcripts and their related cyclin dependent kinases: Cdk2, Cdk4, and Cdk6. The higher doses of ASPE initiated a dose-dependent apoptotic death in MDA-MB-231 by induction of Bax transcripts, inhibition of Bcl-2 and cleavage of Caspase-3 protein. Over-generation of reactive oxygen species (ROS) were also observed in MDA-MB-231 treated cells.
  
  
  CONCLUSIONS
  These findings indicated that ASPE induces G1-phase arrest and apoptosis in MDA-MB-231 cells. ASPE may serve as a potential therapeutic agent for breast cancer.
authors.affiliation: Division of Human Genetics, Department of Molecular Biology and Biotechnology, AECS, P. O. Box 6091, Damascus, Syria.
authors.forename: Hossam
authors.initials: H
authors.lastname: Murad
authors.affiliation: Division of Biochemistry & Toxicology, Department of Molecular Biology and Biotechnology, Damascus, Syria.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Hawat
authors.affiliation: Division of Mammalian Biology, Department of Molecular Biology and Biotechnology, Damascus, Syria.
authors.forename: Adnan
authors.initials: A
authors.lastname: Ekhtiar
authors.affiliation: Division of Mammalian Biology, Department of Molecular Biology and Biotechnology, Damascus, Syria.
authors.forename: Abdulmunim
authors.initials: A
authors.lastname: AlJapawe
authors.affiliation: Laboratory of Marine biology, Faculty of Sciences, Tishreen University, Lattakia, Syria.
authors.forename: Assef
authors.initials: A
authors.lastname: Abbas
authors.affiliation: Division of Human Genetics, Department of Molecular Biology and Biotechnology, AECS, P. O. Box 6091, Damascus, Syria.
authors.forename: Hussein
authors.initials: H
authors.lastname: Darwish
authors.affiliation: Laboratory of plant functional genomics, Department of Molecular Biology and Biotechnology, AECS, P. O. Box 6091, Damascus, Syria.
authors.forename: Oula
authors.initials: O
authors.lastname: Sbenati
authors.affiliation: Laboratory of plant functional genomics, Department of Molecular Biology and Biotechnology, AECS, P. O. Box 6091, Damascus, Syria.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Ghannam
keywords: Apoptosis; G1-phase cell cycle arrest; MDA-MB-231; Red algae