Planta Med 2023; 89(03): 286-294
DOI: 10.1055/a-1910-5776
Biological and Pharmacological Activity
Original Papers

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

Silvia de Maria Souza
1   Department of Physiology and Pharmacology, Biosciences Center, Federal University of Pernambuco, Recife-Pernambuco, Brazil
,
Luciano Santos de Souza
2   Gonçalo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ/BA), Salvador-Bahia, Brazil
,
Valdenizia Rodrigues Silva
2   Gonçalo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ/BA), Salvador-Bahia, Brazil
,
Milena Botelho Pereira Soares
2   Gonçalo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ/BA), Salvador-Bahia, Brazil
3   SENAI Institute for Innovation in Advanced Health Systems, SENAI CIMATEC, Salvador-Bahia, Brazil
,
Daniel Pereira Bezerra
2   Gonçalo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ/BA), Salvador-Bahia, Brazil
,
Roberto Wagner da Silva Gois
4   Federal Institute of Ceara, Campus Acaraú, Acaraú-Ceara, Brazil
5   Chemistry Postgraduate Program, Federal University of Ceara, Fortaleza-Ceara, Brazil
,
Horlando Carlota da Silva
5   Chemistry Postgraduate Program, Federal University of Ceara, Fortaleza-Ceara, Brazil
,
Gilvandete Maria Pinheiro Santiago
5   Chemistry Postgraduate Program, Federal University of Ceara, Fortaleza-Ceara, Brazil
6   Department of Pharmacy, Federal University of Ceara, Fortaleza-Ceara, Brazil
,
Gardenia Carmen Gadelha Militao
1   Department of Physiology and Pharmacology, Biosciences Center, Federal University of Pernambuco, Recife-Pernambuco, Brazil
› Author Affiliations
Supported by: FACEPE 1133-2.07/2012

Abstract

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 IC50 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 (IC50 > 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.

Supporting Information



Publication History

Received: 04 March 2022

Accepted after revision: 27 July 2022

Accepted Manuscript online:
27 July 2022

Article published online:
23 August 2022

© 2022. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
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