Apoptosis inducing metabolite from marine mangrove actinobacteria VITGAP173

Ajitha Gomathi; Manikandan Alagumuthu; Pavan Kumar Jgs; Harishkumar Madhyastha; Rama Jayaraj; K M Gothandam

doi:10.2174/1871520622666220523155905

Apoptosis inducing metabolite from marine mangrove actinobacteria VITGAP173

Anticancer Agents Med Chem. 2022 May 23. doi: 10.2174/1871520622666220523155905. Online ahead of print.

Authors

Ajitha Gomathi^{1

2}, Manikandan Alagumuthu¹, Pavan Kumar Jgs^{1

2}, Harishkumar Madhyastha³, Rama Jayaraj⁴, K M Gothandam¹

Affiliations

¹ Department of Biotechnology, School of Bio Sciences and Technology, Vellore Institute of Technology (VIT), Vellore - 14, Tamil Nadu, India.
² Department of Biotechnology, The Oxford College of Engineering, Bengaluru- 560068, India.
³ Department of Applied Physiology, Faculty of Medicine, University of Miyazaki, Miyazaki. 889-1692, Japan.
⁴ Theme Lead, Flinders NT, Flinders University, Northern Territory 0909, Australia.

PMID: 35616681
DOI: 10.2174/1871520622666220523155905

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. 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.

Conclusion: The present findings suggest the apoptosis inducing potential of fraction-2 in breast cancer therapy.

Keywords: ER stress; Mangrove; actinobacteria; apoptosis; bioactive fraction; cytotoxic.