The effect of Tamoxifen on the expression of antioxidant genes Superoxide Dismutase 2 and Glutathione Peroxidase 1 in the presence and absence of antioxidants

Faraji, Shadi; Seyfahmadi, Mahdi; Gholinejad, Zafar

doi:10.48307/bcbn.2025.560243.1041

The effect of Tamoxifen on the expression of antioxidant genes Superoxide Dismutase 2 and Glutathione Peroxidase 1 in the presence and absence of antioxidants

Document Type : Original Article

Authors

Shadi Faraji ¹

Mahdi Seyfahmadi ¹

Zafar Gholinejad ²

¹ Department of Biology, Ur.C., Islamic Azad University, Urmia, Iran

² Department of Medical Laboratory Sciences, Ur.C., Islamic Azad University, Urmia, Iran AND Biotechnology Research Center, Ur.C., Islamic Azad University, Urmia, Iran

10.48307/bcbn.2025.560243.1041

Abstract

Background: Tamoxifen (TAM) is a first-line therapy for estrogen receptor-positive breast cancer, exerting part of its anticancer effect through the induction of oxidative stress. Despite its widespread clinical use, the precise impact of TAM on the cellular antioxidant defense system remains incompletely understood.
Objectives: This study aimed to investigate the effect of TAM on the expression of key antioxidant genes, Superoxide Dismutase 2 (SOD2) and Glutathione Peroxidase 1 (GPx1), and to assess whether the antioxidants Vitamins C and E can modulate this response.
Methods: Human MCF-7 breast cancer cells were treated with 2 µM TAM, either alone or in combination with Vitamin C (Vit C, 50 µM) and/or Vitamin E (Vit E, 16 µM), for 6 and 24 hours. Total Antioxidant Capacity (TAC) was measured using the FRAP assay. The mRNA expression of SOD2 and GPx1 was quantified by real-time polymerase chain reaction (qRT-PCR).
Results: Exposure to TAM for 24 hours significantly reduced TAC while simultaneously upregulating SOD2 and GPx1 mRNA expression. Co-treatment with Vit E effectively attenuated the TAM-induced suppression of SOD2 and restored TAC to near baseline levels. Vit C demonstrated a similar, though less pronounced, effect. Interestingly, the combined administration of both vitamins did not produce a synergistic benefit and was not superior to Vit E alone in mitigating TAM-induced oxidative stress.
Conclusion: TAM induces notable oxidative stress in MCF-7 cells within 6 hours, yet upregulation of antioxidant enzymes contributes to a partial recovery in TAC after 24 hours. Vit E, and to a lesser extent Vit C, can counteract TAM-induced oxidative stress, while the absence of synergy between the two antioxidants suggests that a single, well-chosen antioxidant may suffice to mitigate these effects. These findings have potential implications for optimizing adjuvant antioxidant therapy in patients undergoing TAM treatment.

Keywords

Tamoxifen

Superoxide Dismutase 2 (SOD2)

Glutathione Peroxidase 1 (GPx1)

Vitamin E

Vitamin C

Breast cancer

Subjects