Background Marine microorganisms are considered to be an important source of

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. extracts were found to be cytotoxic against MK-0517 (Fosaprepitant) one or more malignancy cell lines with cell collection specific activities. Out of the 13 most active microbial extracts six extracts were able to induce significantly higher apoptosis (>70%) in malignancy cells. Mechanism level studies revealed that extracts from (P3-86A and P3-86B(2)) followed the sequence of events of apoptotic pathway including MMP disruption caspase-3/7 activity caspase-8 cleavage PARP-1 cleavage and Phosphatidylserine (PS) exposure whereas another extract (K30) induced caspase-9 mediated apoptosis. The extracts from (P3-37B) (K18) and (P3-37C) were unable to induce any switch in MMP in HeLa malignancy 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. Conclusion 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. drug screening. The evaluation of proapoptotic potential of highly cytotoxic extracts further revealed six highly potent extracts that were subjected to more detailed assays to infer the pathways involved in apoptotic mode of cell death in malignancy cells. Methods Field sampling The samples were retrieved from brine-seawater interfaces brine layers and sediments of deep-sea brine pools during KAUST Red Sea Expedition 2011. Water samples were collected using a rosette sampler equipped with 20 Niskin bottles (10 liter each) and a conductivity-temperature-depth (CTD) unit for monitoring salinity heat transmission and pressure (Idronout S.r.l Italy). At each sampling site approximately 180 litres of sample were collected and pre-filtered through a 5.0?μm SMWP membrane (diameter 290?mm; Millipore Ireland) to remove suspended particles. A tangential circulation filtration (TFF) system (Pellicon 2 Filter Acrylic Holder Millipore US) was used in MK-0517 (Fosaprepitant) order to filter-concentrate the MK-0517 (Fosaprepitant) samples. One liter of each concentrated sample was obtained after retention through a Durapore 0.1?μm PVDF filter (Pellicon 2 Cassette Filter Screen type C size 0.5?m2 Millipore Corporation MA USA). These concentrated samples were stored in a dark bottle at MAT1 4°C and used as inoculum for microbial isolations. Sediment collection was performed by deploying a multicore sampling device into the bottom of the brine pools. The top layer of sediment (approximately 10?cm) was slice kept in anoxic containers in the dark and were later used as inoculum for microbial isolations. Source of bacterial isolates A total of 24 bacterial strains were successfully isolated from deep-sea brine pools of the Red Sea. Nineteen of them were isolated from brine-seawater interfaces one strain from brine and four strains from sediments (Table?1). The inocula for bacterial isolation were collected from five different brine pools named Atlantis II (2194?m) Discovery Deep (2224?m) Kebrit Deep (1573?m) Nereus Deep (2458?m) and Erba Deep (2395?m) [19]. Each of the deep-sea brine pools has its unique physicochemical composition with salinity up to 26% including notably high temperature as well as high concentrations of heavy metals [20]. The Atlantis II Deep and the Discovery deep are considered as warm brines with maximum temperatures 67.8°C and 44.8°C respectively. Brine-seawater boundaries in these brine pools are characterized by strong heat and salinity gradients [21]. Table 1 Taxonomic identification and collection location for 24 microbial strains All of the bacterial strains isolated in this study were obtained by the streak plate method described elsewhere [34]. Eighteen strains grew MK-0517 (Fosaprepitant) in salinities of 10% NaCl and the rest of the isolates grew well in salinities of 20% NaCl. PCR amplification Nucleic acids were.