Assessment of the cytotoxic, proapoptotic, and genotoxic effects of bromelain on human peripheral blood mononuclear cells

Bromelain, a proteolytic enzyme from pineapple, is a promising anticancer candidate due to its ability to induce apoptosis in various malignant cell lines. While its antitumor efficacy is explored, the safety profile of bromelain in normal human cells requires further validation to support its clinical application. This study examines the cytotoxic, proapoptotic, and genotoxic effects of bromelain at concentrations ranging from 0 to 120 µg/mL on normal human peripheral blood mononuclear cells (PBMCs). The following assessments were conducted: cell survival, protein integrity (thiol and amino groups), mitochondrial membrane potential, types of cell death, and DNA damage. The results indicate that bromelain at the studied concentrations exhibits low overall cytotoxicity toward PBMCs. While it did not cause nonspecific proteolysis of cellular proteins, bromelain at concentrations of 60 and 120 µg/mL triggered apoptosis (9.8% and 15.08%, respectively). The proapoptotic effect observed at 120 µg/mL in PBMCs was associated with several factors: decreased mitochondrial membrane potential, increased expression of proapoptotic caspases-9 and − 3, the proapoptotic protein Bax, and subsequent PARP cleavage. Furthermore, bromelain demonstrated dose-dependent genotoxic effects in PBMCs across the entire tested range (30–120 µg/mL), with a maximum DNA damage of 16.0% in the comet tail. These findings highlight the concentration-dependent response of human PBMCs to bromelain and provide important safety data that should be considered when evaluating its potential as a therapeutic agent.