title: Induction of apoptosis in cancer cell lines by the Red Sea brine pool bacterial extracts.
abstract: BACKGROUND
  Marine microorganisms are considered to be an important source of bioactive molecules against various diseases and have great potential to increase the number of lead molecules in clinical trials. Progress in novel microbial culturing techniques as well as greater accessibility to unique oceanic habitats has placed the marine environment as a new frontier in the field of natural product drug discovery.
  
  
  METHODS
  A total of 24 microbial extracts from deep-sea brine pools in the Red Sea have been evaluated for their anticancer potential against three human cancer cell lines. Downstream analysis of these six most potent extracts was done using various biological assays, such as Caspase-3/7 activity, mitochondrial membrane potential (MMP), PARP-1 cleavage and expression of γH2Ax, Caspase-8 and -9 using western blotting.
  
  
  RESULTS
  In general, most of the microbial extracts were found to be cytotoxic against one or more cancer cell lines with cell line specific activities. Out of the 13 most active microbial extracts, six extracts were able to induce significantly higher apoptosis (>70%) in cancer cells. Mechanism level studies revealed that extracts from Chromohalobacter salexigens (P3-86A and P3-86B(2)) followed the sequence of events of apoptotic pathway involving MMP disruption, caspase-3/7 activity, caspase-8 cleavage, PARP-1 cleavage and Phosphatidylserine (PS) exposure, whereas another Chromohalobacter salexigens extract (K30) induced caspase-9 mediated apoptosis. The extracts from Halomonas meridiana (P3-37B), Chromohalobacter israelensis (K18) and Idiomarina loihiensis (P3-37C) were unable to induce any change in MMP in HeLa cancer cells, and thus suggested mitochondria-independent apoptosis induction. However, further detection of a PARP-1 cleavage product, and the observed changes in caspase-8 and -9 suggested the involvement of caspase-mediated apoptotic pathways.
  
  
  CONCLUSIONS
  Altogether, the study offers novel findings regarding the anticancer potential of several halophilic bacterial species inhabiting the Red Sea (at the depth of 1500-2500 m), which constitute valuable candidates for further isolation and characterization of bioactive molecules.
authors.forename: Sunil
authors.initials: S
authors.lastname: Sagar
authors.forename: Luke
authors.initials: L
authors.lastname: Esau
authors.forename: Karie
authors.initials: K
authors.lastname: Holtermann
authors.forename: Tyas
authors.initials: T
authors.lastname: Hikmawan
authors.forename: Guishan
authors.initials: G
authors.lastname: Zhang
authors.forename: Ulrich
authors.initials: U
authors.lastname: Stingl
authors.forename: Vladimir B
authors.initials: VB
authors.lastname: Bajic
authors.affiliation: Computational Bioscience Research Center, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Kingdom of Saudi Arabia. mandeep.kaur@kaust.edu.sa.
authors.forename: Mandeep
authors.initials: M
authors.lastname: Kaur
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D059001:Aquatic Organisms / Q000737:chemistry; D001688:Biological Products / Q000494:pharmacology*; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005434:Flow Cytometry; D044129:Halomonadaceae / Q000737:chemistry* / Q000302:isolation & purification; D006657:Histones / Q000378:metabolism; D006801:Humans; D019156:Indian Ocean; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D014871:Water Microbiology
chemical_list: D000970:Antineoplastic Agents; D001688:Biological Products; C468783:H2AX protein, human; D006657:Histones; D011065:Poly(ADP-ribose) Polymerases; D020169:Caspases