title: Anti-cancer effects of blue-green alga Spirulina platensis, a natural source of bilirubin-like tetrapyrrolic compounds.
abstract: Spirulina platensis is a blue-green alga used as a dietary supplement because of its hypocholesterolemic properties. Among other bioactive substances, it is also rich in tetrapyrrolic compounds closely related to bilirubin molecule, a potent antioxidant and anti-proliferative agent. The aim of our study was to evaluate possible anticancer effects of S. platensis and S. platensis-derived tetrapyrroles using an experimental model of pancreatic cancer. The anti-proliferative effects of S. platensis and its tetrapyrrolic components [phycocyanobilin (PCB) and chlorophyllin, a surrogate molecule for chlorophyll A] were tested on several human pancreatic cancer cell lines and xenotransplanted nude mice. The effects of experimental therapeutics on mitochondrial reactive oxygen species (ROS) production and glutathione redox status were also evaluated. Compared to untreated cells, experimental therapeutics significantly decreased proliferation of human pancreatic cancer cell lines in vitro in a dose-dependent manner (from 0.16 g•L-1 [S. platensis], 60 μM [PCB], and 125 μM [chlorophyllin], p<0.05). The anti-proliferative effects of S. platensis were also shown in vivo, where inhibition of pancreatic cancer growth was evidenced since the third day of treatment (p < 0.05). All tested compounds decreased generation of mitochondrial ROS and glutathione redox status (p = 0.0006; 0.016; and 0.006 for S. platensis, PCB, and chlorophyllin, respectively). In conclusion, S. platensis and its tetrapyrrolic components substantially decreased the proliferation of experimental pancreatic cancer. These data support a chemopreventive role of this edible alga. Furthermore, it seems that dietary supplementation with this alga might enhance systemic pool of tetrapyrroles, known to be higher in subjects with Gilbert syndrome.
authors.affiliation: Institute of Medical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University, Prague, Czech Republic.
authors.forename: Renata
authors.initials: R
authors.lastname: Koníčková
authors.affiliation: Institute of Medical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University, Prague, Czech Republic.
authors.forename: Kateřina
authors.initials: K
authors.lastname: Vaňková
authors.affiliation: Institute of Medical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University, Prague, Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Vaníková
authors.affiliation: Institute of Medical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University, Prague, Czech Republic.
authors.forename: Kateřina
authors.initials: K
authors.lastname: Váňová
authors.affiliation: Institute of Medical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University, Prague, Czech Republic.
authors.forename: Lucie
authors.initials: L
authors.lastname: Muchová
authors.affiliation: Institute of Medical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University, Prague, Czech Republic.
authors.forename: Iva
authors.initials: I
authors.lastname: Subhanová
authors.affiliation: Institute of Biophysics, 1st Faculty of Medicine, Charles University, Prague, Czech Republic.
authors.forename: Marie
authors.initials: M
authors.lastname: Zadinová
authors.affiliation: Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Zelenka
authors.affiliation: Institute of Medical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University, Prague, Czech Republic.
authors.forename: Aleš
authors.initials: A
authors.lastname: Dvořák
authors.affiliation: Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
authors.forename: Michal
authors.initials: M
authors.lastname: Kolář
authors.affiliation: Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
authors.forename: Hynek
authors.initials: H
authors.lastname: Strnad
authors.affiliation: Department of Biochemistry and Microbiology, Institute of Chemical Technology, Prague, Czech Republic.
authors.forename: Silvie
authors.initials: S
authors.lastname: Rimpelová
authors.affiliation: Department of Biochemistry and Microbiology, Institute of Chemical Technology, Prague, Czech Republic.
authors.forename: Tomáš
authors.initials: T
authors.lastname: Ruml
authors.affiliation: Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Ronald
authors.initials: R
authors.lastname: J Wong
authors.affiliation: Institute of Medical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University, Prague, Czech Republic; 4th Department of Internal Medicine, 1st Faculty of Medicine, Charles University, Prague, Czech Republic.
authors.forename: Libor
authors.initials: L
authors.lastname: Vítek
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001663:Bilirubin / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008819:Mice, Nude; D010084:Oxidation-Reduction; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D010936:Plant Extracts / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D053545:Spirulina; D045725:Tetrapyrroles / Q000494:pharmacology*; D014183:Transplantation, Heterologous; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D045725:Tetrapyrroles; D005978:Glutathione; D001663:Bilirubin