A differential study on oxidized/reduced ascorbic acid induced tumor cells' apoptosis under hypoxia

Area of Science:

• Biomedical Engineering
• Cancer Biology
• Nanotechnology

Background:

• Ascorbic acid (AA) and its oxidized form (DHA) have potential anticancer properties.
• Understanding their distinct mechanisms is crucial for developing targeted cancer therapies.
• Tumor microenvironments often exhibit hypoxia and altered redox homeostasis.

Purpose of the Study:

• To investigate the distinct intracellular anticancer mechanisms of AA and DHA.
• To explore their roles in inducing apoptosis pathways within cancer cells.
• To utilize a novel pH-controlled nanocarrier for targeted delivery.

Main Methods:

• Development of a pH-controlled fluorescent silicon nanoparticle for targeted delivery of AA/DHA.
• Delivery of AA/DHA into HepG2 and B16-F10 cancer cells.
• Monitoring of apoptosis via Caspase-3 nanoprobe.
• Assessment of H2O2 and NAD(P)H levels using fluorescent probes under hypoxic conditions.

Main Results:

• AA scavenges H2O2 and promotes NAD(P)H accumulation, inducing reductive stress.
• DHA promotes both H2O2 and NAD(P)H production, enhancing oxidative stress.
• Distinct molecular pathways for AA and DHA-induced apoptosis were identified.

Conclusions:

• AA and DHA exert anticancer effects through significantly different redox mechanisms.
• AA induces reductive stress, while DHA induces oxidative stress in cancer cells.
• Targeted delivery systems can elucidate the differential functions of redox-active molecules in cancer therapy.