A Natural Quinazoline Derivative from Marine Sponge Hyrtios erectus Induces Apoptosis of Breast Cancer Cells via ROS Production and Intrinsic or Extrinsic Apoptosis Pathways.

Autor:	De AK; ICAR-Central Island Agricultural Research Institute, Port Blair 744101, Andaman and Nicobar Islands, India.; Bioinformatics Centre, ICAR-Central Island Agricultural Research Institute, Port Blair 744101, Andaman and Nicobar Islands, India., Muthiyan R; Bioinformatics Centre, ICAR-Central Island Agricultural Research Institute, Port Blair 744101, Andaman and Nicobar Islands, India., Mondal S; Department of Veterinary Pathology, West Bengal University of Animal and Fisheries Sciences, Kolkata 700037, West Bengal, India., Mahanta N; Department of Chemistry and Institute for Genomic Biology, University of Illinois, Urbana Champaign, IL 61801, USA.; Department of Chemistry, Indian Institute of Technology, Dharwad, WALMI campus (near High Court), Bangaluru 580011, Karnataka, India., Bhattacharya D; ICAR-Central Island Agricultural Research Institute, Port Blair 744101, Andaman and Nicobar Islands, India., Ponraj P; ICAR-Central Island Agricultural Research Institute, Port Blair 744101, Andaman and Nicobar Islands, India., Muniswamy K; ICAR-Central Island Agricultural Research Institute, Port Blair 744101, Andaman and Nicobar Islands, India., Kundu A; ICAR-Central Island Agricultural Research Institute, Port Blair 744101, Andaman and Nicobar Islands, India., Kundu MS; ICAR-Central Island Agricultural Research Institute, Port Blair 744101, Andaman and Nicobar Islands, India., Sunder J; ICAR-Central Island Agricultural Research Institute, Port Blair 744101, Andaman and Nicobar Islands, India., Karunakaran D; Division of Social Science, ICAR-Central Island Agricultural Research Institute, Port Blair 744101, Andaman and Nicobar Islands, India., Bera AK; Reservoir and Wetland Fisheries Division, ICAR-Central Inland Fishery Research Institute, Barrackpore, Kolkata 700120, West Bengal, India., Roy SD; Division of Fisheries Sciences, ICAR-Central Island Agricultural Research Institute, Port Blair 744101, Andaman and Nicobar Islands, India., Malakar D; Animal Biotechnology Centre, National Dairy Research Institute, Karnal 132001, Haryana, India.
Jazyk:	angličtina
Zdroj:	Marine drugs [Mar Drugs] 2019 Nov 23; Vol. 17 (12). Date of Electronic Publication: 2019 Nov 23.
DOI:	10.3390/md17120658
Abstrakt:	Here, we report the therapeutic potential of a natural quinazoline derivative (2-chloro-6-phenyl-8H-quinazolino[4,3-b]quinazolin-8-one) isolated from marine sponge Hyrtios erectus against human breast cancer. The cytotoxicity of the compound was investigated on a human breast carcinoma cell line (MCF-7). Antiproliferative activity of the compound was estimated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. MTT assay showed significant inhibition of MCF-7 cells viability with the IC50 value of 13.04 ± 1.03 µg/mL after 48 h. The compound induced down-regulation of anti-apoptotic Bcl-2 protein and increase in the pro-apoptotic Bax/Bcl-2 ratio in MCF-7 cells. The compound activated the expression of Caspases-9 and stimulated downstream signal transducer Caspase-7. In addition, Caspase-8 showed remarkable up-regulation in MCF-7 cells treated with the compound. Moreover, the compound was found to promote oxidative stress in MCF-7 cells that led to cell death. In conclusion, the compound could induce apoptosis of breast carcinoma cells via a mechanism that involves ROS production and either extrinsic or intrinsic apoptosis pathways. The systemic toxic potential of the compound was evaluated in an in vivo mouse model, and it was found non-toxic to the major organs. Competing Interests: The authors declare no conflict of interest.
Databáze:	MEDLINE
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