Ajitha Gomathi, Manikandan Alagumuthu, Pavan Kumar JGS, Harishkumar Madhyastha, Rama Jayaraj and K M Gothandam*
Background: Marine actinobacteria have proven to be a remarkable source of bioactive metabolites. <p> Methods: The present study focused on the isolation of anticancer metabolites from marine actinobacteria. Streptomyces sp. VITGAP173 was found to have promising anticancer activity against breast cancer cell lines (MCF-7). <P> Results: Bioassay-guided fractionation was followed to identify the bioactive metabolites from crude ethyl acetate extract of VITGAP173, which yielded four fractions. Among the four fractions, fraction B exhibited the highest cytotoxic activity against MCF-7 cell lines. Further structural characterization of the fraction was done by FTIR and NMR spectroscopy. The fraction-2 induced cytotoxicity against MCF-7 cell lines and the half maximal inhibition (IC50) value was calculated as 4.7μg/ml. To elucidate the possible mechanism of cell death, MCF-7 cells were treated with fraction-2 for 24 hours and the morphological changes were examined using acridine orange – ethidium bromide (AO/EB) staining. The fraction also increased the reactive oxygen species (ROS) generation (Flow cytometry, DCFH-DA). The molecular mechanism of fraction-induced cell death was analysed by real-time PCR, which revealed that the fraction promotes apoptosis through the CHOP-ATF-4 pathway which is involved in ER stress signalling. <P> Conclusion: The present findings suggest the apoptosis inducing potential of fraction-2 in breast cancer therapy.
Mangrove, actinobacteria, bioactive fraction, cytotoxic, apoptosis, ER stress