Estrogen Receptor β Participates in Alternariol-Induced Oxidative Stress in Normal Prostate Epithelial Cells

Area of Science:

• Environmental toxicology
• Molecular toxicology
• Prostate disease research

Background:

• Alternaria toxins are emerging mycotoxins with incompletely understood human toxicity.
• Alternariol (AOH) is a prevalent Alternaria mycotoxin with known genotoxicity and hormonal effects, but its molecular mechanisms remain unclear.
• Prostate diseases are linked to hormonal imbalances and chronic inflammation, with environmental agents potentially playing a role.

Purpose of the Study:

• To investigate the effects of two doses of Alternariol (AOH) on prostate epithelial cells.
• To elucidate the molecular mechanisms underlying AOH toxicity in the prostate.
• To assess the role of estrogen receptor beta (ERβ) in AOH-induced cellular responses.

Main Methods:

• Exposure of prostate epithelial cells to two doses of AOH (10 µM and 0.1 µM).
• Assessment of oxidative stress, DNA damage, and cell cycle arrest.
• Evaluation of nuclear erythroid-related factor 2 (Nrf2) modulation.
• Use of a selective estrogen receptor beta (ERβ) inhibitor (PHTPP) to determine ERβ involvement.

Main Results:

• The higher dose of AOH (10 µM) induced oxidative stress, DNA damage, and cell cycle arrest, partially mediated by ERβ.
• The lower dose of AOH (0.1 µM) induced only oxidative stress.
• AOH modulated Nrf2 in response to the higher dose.
• AOH-induced oxidative stress was partially dependent on ERβ activation for both doses, but ERβ inhibition did not fully prevent ROS production or DNA damage at the higher AOH dose.

Conclusions:

• This study provides the first evidence that Alternariol (AOH) affects fundamental processes in normal prostate epithelial cells.
• AOH's effects on oxidative stress and DNA damage, potentially involving ERβ, may contribute to benign and malignant prostate tissue changes.
• Further research is warranted to fully understand the implications of AOH exposure for prostate health.