Natural Dibenzo[b,f]oxepines, Pacharin and Bauhiniastatin-1, Isolated from Bauhinia acuruana Induce Apoptosis on Breast Cancer Cells via MCL-1 Protein Reduction.

Autor:	Souza SM; Department of Physiology and Pharmacology, Biosciences Center, Federal University of Pernambuco, Recife-Pernambuco, Brazil., Souza LS; Gonçalo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ/BA), Salvador-Bahia, Brazil., Silva VR; Gonçalo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ/BA), Salvador-Bahia, Brazil., Soares MBP; Gonçalo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ/BA), Salvador-Bahia, Brazil.; SENAI Institute for Innovation in Advanced Health Systems, SENAI CIMATEC, Salvador-Bahia, Brazil., Bezerra DP; Gonçalo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ/BA), Salvador-Bahia, Brazil., Gois RWDS; Federal Institute of Ceara, Campus Acaraú, Acaraú-Ceara, Brazil.; Chemistry Postgraduate Program, Federal University of Ceara, Fortaleza-Ceara, Brazil., Silva HCD; Chemistry Postgraduate Program, Federal University of Ceara, Fortaleza-Ceara, Brazil., Santiago GMP; Chemistry Postgraduate Program, Federal University of Ceara, Fortaleza-Ceara, Brazil.; Department of Pharmacy, Federal University of Ceara, Fortaleza-Ceara, Brazil., Militao GCG; Department of Physiology and Pharmacology, Biosciences Center, Federal University of Pernambuco, Recife-Pernambuco, Brazil.
Jazyk:	angličtina
Zdroj:	Planta medica [Planta Med] 2023 Mar; Vol. 89 (3), pp. 286-294. Date of Electronic Publication: 2022 Jul 27.
DOI:	10.1055/a-1910-5776
Abstrakt:	Herein, we describe the antiproliferative effects of two natural dibenzo [ b,f ]oxepines, pacharin and bauhiniastatin-1, isolated from Bauhinia acuruana on a breast cancer cell line and the mode of action underlying the cytotoxicity. Both compounds were cytotoxic in a panel of six tumor lines analyzed by the MTT assay, and IC 50 values ranged from 7.8 to 45.1 µM, including human breast adenocarcinoma (MCF-7) cells. In contrast, none of the compounds were cytotoxic on normal human peripheral blood mononuclear cells (IC 50 > 100 µM). Human breast adenocarcinoma (MCF-7) cells treated with pacharin or bauhiniastatin-1 20 µM for 24 h presented a reduction in cell volume and intensification of chromatin condensation, DNA fragmentation, and apoptotic cells. These findings became more evident after 48 h of exposure. Antiapoptotic B-cell lymphoma-2 family members, such as myeloid cell leukemia-1 and B-cell lymphoma-extra large, are important targets in cancer cells since their overexpression confers resistance to cancer treatments. A significant reduction of the myeloid cell leukemia-1 protein levels in human breast adenocarcinoma (MCF-7) cells after 24 h of treatment with pacharin or bauhiniastatin-1 at 20 µM was observed, while the B-cell lymphoma-extra large protein content was reduced in bauhiniastatin-1-treated cells at 40 µM only. The cytotoxic effects of pacharin and bauhiniastatin-1 are likely linked to myeloid cell leukemia-1 inhibition, which leads to the apoptosis of breast adenocarcinoma cells. Competing Interests: The authors declare that they have no conflict of interest. (Thieme. All rights reserved.)
Databáze:	MEDLINE
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