Estradiol Reshapes Cell-Type-Dependent Basal Redox Set-Points in Colorectal Carcinoma Cells

Area of Science:

• Cellular biology
• Cancer research
• Biochemistry

Background:

• Redox balance is crucial for colorectal cancer cell survival.
• Estradiol, an antioxidant, is linked to lower colorectal cancer incidence.
• Understanding cellular redox responses to estradiol is key for cancer therapy.

Purpose of the Study:

• To evaluate adaptive and maladaptive redox responses of colorectal cancer cells to estradiol.
• To define the basal redox set-point as the intracellular balance of oxidants and antioxidants.
• To explore the link between redox set-point organization and estradiol responsiveness.

Main Methods:

• Human colorectal cancer cell lines (HCT-116, SW-480) were treated with estradiol.
• Analysis of redox biomarkers (superoxide anion, hydrogen peroxide, nitric oxide, glutathione), cell viability, and migration.
• Application of correlation, network topology, PCA, and Jaccard similarity analyses.

Main Results:

• HCT-116 cells showed an O2.--centered redox set-point; estradiol induced antioxidant activation and reduced proliferation (maladaptive).
• SW-480 cells displayed a H2O2-centered redox set-point; estradiol modulated NO and GSH, increasing proliferation (adaptive).
• Redox set-point organization differed between cell lines and influenced estradiol response.

Conclusions:

• Redox set-point organization may determine colorectal cancer cell responsiveness to estradiol.
• Characterizing basal redox set-points could stratify patients for redox-modulating therapies.
• This approach may inform personalized treatment strategies for colorectal cancer.