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

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 mu M, 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 mu M). Human breast adenocarcinoma (MCF-7) cells treated with pacharin or bauhiniastatin-1 20 mu M 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 mu M was observed, while the B-cell lymphoma-extra large protein content was reduced in bauhiniastatin-1-treated cells at 40 mu M 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.

Automated summary

In this study, the antiproliferative effects of two natural compounds, pacharin and bauhiniastatin-1, isolated from Bauhinia acuruana on breast cancer cells were investigated. The results showed that both compounds exhibited cytotoxicity against various tumor cell lines, including human breast adenocarcinoma, while having no toxicity on normal cells. The mechanism of action was found to be related to the inhibition of myeloid cell leukemia-1 protein, leading to apoptosis of breast adenocarcinoma cells.