Apoptosis and lysosome membrane permeabilization induction on breast cancer cells by an anticarcinogenic Bowman-Birk protease inhibitor from Vigna unguiculata seeds.
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.
Department of Genetics and Morphology, University of Brasília, Asa Norte, Brazil; Department of Cell Biology, University of Brasília, Asa Norte, Brazil.
Graziella Anselmo
GA
Joanitti
Ricardo Bentes
RB
Azevedo
Sonia Maria
SM
Freitas
D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D007887:Fabaceae / Q000737:chemistry*; D005260:Female; D006801:Humans; D008247:Lysosomes / Q000187:drug effects* / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008856:Microscopy, Fluorescence; D010940:Plant Proteins / Q000302:isolation & purification / Q000494:pharmacology; D012639:Seeds / Q000737:chemistry; D014361:Trypsin Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*
D010940:Plant Proteins; D014361:Trypsin Inhibitors; C042736:trypsin, chymotrypsin inhibitor, black-eyed pea