Apoptosis and lysosome membrane permeabilization induction on breast cancer cells by an anticarcinogenic Bowman–Birk protease inhibitor from Vigna unguiculata seeds
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Abstract
In this work, we report the effects of a Bowman-Birk protease inhibitor, the Black-Eyed
Pea Trypsin/Chymotrypsin Inhibitor - BTCI, purified from Vigna unguiculata seeds,
on the MCF-7 breast cancer cells. The treatment of MCF-7 with 200microM BTCI for 72h
induced significant reduction of the cell viability and proliferation (arrest in S
and G2/M phase). These cytostatic effects were accompanied by acute morphological
modifications including the alteration of the nuclear morphology, plasma membrane
fragmentation, cytoplasm disorganization, presence of double-membrane vesicles, mitochondrial
swelling, and an increase in the size of lysosomes. Significative DNA fragmentation,
annexin-V(+) cell number increase, mitochondrial membrane potential reduction, and
cytoplasm acidification were also detected. All together, these cytostatic and cytotoxic
results point out to BTCI-induced apoptosis cell death associated with severe cell
morphological alterations and lysosome membrane permeabilization. Our study confirms
the anticarcinogenic potential of Bowman-Birk protease inhibitors and identifies BTCI
as a promising tool for drug developments aimed at the treatment of breast cancer.