Targeting superoxide dismutase 1 to overcome cisplatin resistance in human ovarian cancer
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Updated: Jul 3, 2026
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Published on: August 2, 2024
Dawn P G Brown1, Helen Chin-Sinex, Bei Nie
1Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Purpose:
Clinical drug resistance to platinum-based chemotherapy is considered a major impediment in the treatment of human ovarian cancer. Multiple pathways associated with drug resistance have been suggested by many previous studies. Over expression of several key proteins involved in DNA repair, drug transport, redox regulation, and apoptosis has been recently reported by our group using a global quantitative proteomic profiling approach. Superoxide dismutase 1 (SOD1) is one of these proteins consistently over-expressed in cisplatin-resistant ovarian cancer cells as compared to their sensitive counterparts, but its precise role in drug resistance is yet to be defined.
Method:
In the current study, we examined the role of SOD1 in drug resistance by inhibiting its redox activity in cisplatin-resistant ovarian cancer cells using a small-molecule inhibitor, triethylenetetramine (TETA). The effect of TETA was determined by the cell proliferation assay, clonogenic cell survival assay, and SOD1 activity assay.
Results:
The inhibition of the SOD1 activity enhanced the cisplatin sensitivity in the resistant cells supporting the hypothesis that SOD1 is a key determinant of cisplatin resistance and is an exploitable target to overcome cisplatin drug resistance.
Conclusion:
SOD1 plays an important role in cisplatin resistance and modulation of its activity may overcome this resistance and ultimately lead to improved clinical outcomes.
Insights
Superoxide dismutase 1 (SOD1) drives cisplatin resistance in ovarian cancer. Inhibiting SOD1 activity restores sensitivity to chemotherapy, offering a new therapeutic target for improving patient outcomes.
Area of Science:
- Biochemistry
- Oncology
- Molecular Biology
Background:
- Platinum-based chemotherapy resistance is a major challenge in ovarian cancer treatment.
- Proteomic profiling identified Superoxide Dismutase 1 (SOD1) as over-expressed in cisplatin-resistant ovarian cancer cells.
- The specific role of SOD1 in mediating drug resistance remains largely undefined.
Purpose of the Study:
- To investigate the role of SOD1 in conferring cisplatin resistance in ovarian cancer cells.
- To determine if inhibiting SOD1 activity can restore sensitivity to cisplatin chemotherapy.
Main Methods:
- Utilized a small-molecule inhibitor, triethylenetetramine (TETA), to inhibit SOD1 redox activity.
- Assessed the impact of TETA on cisplatin sensitivity using cell proliferation and clonogenic survival assays.
- Measured SOD1 activity to confirm inhibition.
Main Results:
- Inhibition of SOD1 activity significantly enhanced cisplatin sensitivity in resistant ovarian cancer cells.
- These findings support SOD1 as a key determinant of cisplatin resistance.
- SOD1 represents a potential therapeutic target for overcoming drug resistance.
Conclusions:
- SOD1 plays a critical role in the development of cisplatin resistance in ovarian cancer.
- Modulating SOD1 activity holds promise for overcoming chemoresistance.
- Targeting SOD1 may lead to improved clinical outcomes for ovarian cancer patients.
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