Title:Apoptosis-inducing Metabolite from Marine Mangrove Actinobacteria VITGAP173
Volume: 24
Issue: 13
Author(s): Ajitha Gomathi, Manikandan Alagumuthu, Pavan K.J.G. Sai, Harishkumar Madhyastha, Rama Jayaraj and Gothandam K. Muthukailannan*
Affiliation:
- Department of Biotechnology, School of BioSciences and Technology, Vellore Institute of Technology (VIT), Vellore - 14, Tamil
Nadu, India
Keywords:
Mangrove, actinobacteria, bioactive fraction, cytotoxic, apoptosis, ER stress.
Abstract:
Background: Marine actinobacteria have proven to be a remarkable source of bioactive metabolites.
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).
Results: Bioassay-guided fractionation was followed to identify the bioactive metabolites from crude ethyl acetate
extract of VITGAP173, which yielded four fractions. Fraction B exhibited the highest cytotoxic activity against MCF-7
cell lines among the four fractions. 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 4.7 μg/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, DCFHDA).
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 involved in ER stress signalling.
Conclusion: The present findings suggested the apoptosis-inducing potential of fraction-2 in breast cancer therapy.
