Depolarization of mitochondrial membrane and generation of reactive oxygen species: mechanism of Sorbitol induced apoptotic cell death in human tumoral and non-tumoral cells

In vitro cytotoxicity of sorbitol

Abstract

Literature on the cytotoxicity of sorbitol is limited and contradictory. In this study, organelle-specific cytotoxicity of 10-70 mg/mL of sorbitol using Alamar blue (for mitochondrial activity) and Neutral red (for lysosomal activity) in the human epithelial non-tumor cell, HEK 293, and tumor cell, MCF 7, was investigated. A comparative evaluation of the potential anti-tumor effect of sorbitol and doxorubicin, a known breast cancer drug, on MCF 7 cell line was also carried out. The molecular mechanisms underlining the induced cytotoxicity were studied through cell cycle analysis, detection of reactive oxygen species, and alterations in mitochondrial membrane potential. Double staining with acridine orange and ethidium bromide was also used to further confirm apoptosis/necrosis. The results showed that sorbitol is cytotoxic to non-tumor cells. However, the selectivity index showed that sorbitol is selectively cytotoxic to tumor cells, a chemotherapeutic potential not sufficiently explored so far. A synergistic probable anti-tumor effect of sorbitol in combination with doxorubicin was found. Apoptosis caused by disturbances in the membrane potential of the mitochondria and reactive oxygen species were the probable sorbitol mechanisms of action. Further studies are required so as to safeguard the public health against indiscriminate consumption of sorbitol, and to further elucidate its potential as an anticancer agent.