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Anti-Cancer Agents in Medicinal Chemistry

Author(s): Ajitha Gomathi, Manikandan Alagumuthu, Pavan K.J.G. Sai, Harishkumar Madhyastha, Rama Jayaraj and Gothandam K. Muthukailannan*

DOI: 10.2174/1871520622666220523155905

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Apoptosis-inducing Metabolite from Marine Mangrove Actinobacteria VITGAP173

Page: [1009 - 1015] Pages: 7

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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.

Keywords: Mangrove, actinobacteria, bioactive fraction, cytotoxic, apoptosis, ER stress

Graphical Abstract

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