Following anticancer drug activity in cell lysates with DNA devices

Area of Science:

• Biomedical Engineering
• Cancer Research
• Electrochemistry

Background:

• Understanding anticancer drug selectivity and mechanisms is crucial for effective cancer therapy.
• NAD(P)H:quinone oxidoreductase 1 (NQO1) is an enzyme overexpressed in many cancers, making it a target for bioactivatable drugs.
• Triple-negative breast cancer (TNBC) cell lines offer a model to study NQO1-dependent drug activity.

Purpose of the Study:

• To develop and validate electrochemical DNA devices for tracking the activity and selectivity of the NQO1-bioactivatable drug, β-lapachone.
• To correlate drug-induced DNA damage with cell death in cancer cells with varying NQO1 expression levels.
• To assess the potential of these devices in informing therapeutic decisions for cancer treatment.

Main Methods:

• Utilized multi-electrode chips with electrochemically-active DNA monolayers.
• Prepared cancer cell lysates from MDA-MB-231 (TNBC) cell lines, differing in NQO1 enzyme expression (NQO1+ and NQO1-).
• Tracked electrochemical DNA signal changes in response to β-lapachone exposure to quantify drug-induced DNA damage.

Main Results:

• Electrochemical DNA devices demonstrated a 3.7-fold difference in response between NQO1+ and NQO1- cell lysates.
• The devices showed 10-20 fold selectivity compared to control agents (catalase, dicoumarol) that inhibit DNA damaging pathways.
• Concentration-dependent studies established correlations between β-lapachone concentrations, cell death onset, and DNA damage levels.

Conclusions:

• Electrochemical DNA devices can effectively monitor the activity and selectivity of NQO1-dependent anticancer drugs like β-lapachone.
• These devices show potential for real-time assessment of drug-induced DNA damage and correlation with cell viability.
• The findings suggest that electrochemical DNA biosensors could aid in optimizing cancer therapeutic strategies.