title: Carrageenan delays cell cycle progression in human cancer cells in vitro demonstrated by FUCCI imaging.
abstract: BACKGROUND
  Carrageenan is a sulfated polysaccharide that exists in red seaweeds recently shown to have anticancer properties. Previous findings show various effects of carrageenan suppressing tumor cell growth. One of the hallmarks of cancer is uncontrolled proliferation, a consequence of loss of normal cell-cycle control, that underlies tumor growth. Recently there is an increasing interest in potential anticancer agents that affect cell cycle in cancer cells. Thus, in this study we investigated the effects of carrageenan on the tumor cell cycle.
  
  
  METHODS
  Using human cervical carcinoma cells (HeLa) cells as and human umbilical vein endothelial cells (HUVEC), the cytotoxic effects of kappa carrageenan (k-CO) and lambda carrageenan (λ-CO) at the concentrations of 250-2500 μg/mL were observed. Cell viability was determined using the MTT assay while cell death rates were determined using staining with calcein-AM/propidium iodide. Cell-cycle profile and progression were demonstrated with HeLa cells expressing FUCCI (fluorescence ubiquitination-based cell-cycle indicator) probes (HeLa-FUCCI).
  
  
  RESULTS
  Carrageenan had no significant effect on HUVEC (normal cells). In contrast both forms of carrageenan were cytotoxic towards HeLa cells (cancer cells). Furthermore, according to cell-cycle analysis with FUCCI cells, the cell cycle of HeLa cells was delayed in specific phases due to different carrageenan treatments.
  
  
  CONCLUSIONS
  Considering these results, it could be suggested that carrageenan affects the cell-cycle of HeLa cells not only by arresting the cell cycle in specific phases but also by delaying the time needed for the cell to progress through the cell cycle. Additionally, different types of carrageenans have different effects on cell cycle progression. This effect of carrageenan towards cancer cells could possibly be developed into a tumor cell-specific anticancer agent.
authors.affiliation: Department of Cellular and Integrative Physiology, Fukushima Medical University, Fukushima, Japan. ekaprsdy@fmu.ac.jp.|Faculty of Mathematics and Natural Science, Mataram University, Mataram, Indonesia. ekaprsdy@fmu.ac.jp.
authors.forename: Eka Sunarwidhi
authors.initials: ES
authors.lastname: Prasedya
authors.affiliation: Department of Cellular and Integrative Physiology, Fukushima Medical University, Fukushima, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Miyake
authors.affiliation: Department of Cellular and Integrative Physiology, Fukushima Medical University, Fukushima, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kobayashi
authors.affiliation: Department of Cellular and Integrative Physiology, Fukushima Medical University, Fukushima, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Hazama
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002351:Carrageenan / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D005456:Fluorescent Dyes; D006367:HeLa Cells; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008856:Microscopy, Fluorescence / Q000379:methods*; D015336:Molecular Probe Techniques
chemical_list: D000970:Antineoplastic Agents; D005456:Fluorescent Dyes; D002351:Carrageenan
keywords: Algae; Cancer; Carrageenan; Cell cycle; Fluorescence ubiquitination-based cell-cycle indicator; Human cervical carcinoma cells; Human umbilical vein endothelial cells