3,3'-Diindolylmethane and genistein decrease the adverse effects of estrogen in LNCaP and PC-3 prostate cancer cells

Area of Science:

• Oncology
• Endocrinology
• Phytochemistry

Background:

• 17beta-estradiol (E2) is implicated in prostate cancer (PCa) risk.
• Phytochemicals like genistein (soy) and 3,3'-diindolylmethane (DIM) (cruciferous vegetables) may offer protection against PCa.
• Investigating the interaction between E2 and these phytochemicals is crucial for understanding PCa prevention.

Purpose of the Study:

• To evaluate the capacity of genistein and DIM to mitigate the adverse effects of E2 on PCa.
• To explore the impact of genistein and DIM on E2-mediated proliferation and androgen receptor signaling in PCa cells.
• To analyze the influence of genistein and DIM on E2 metabolism pathways relevant to PCa.

Main Methods:

• Utilized LNCaP (E2-sensitive) and PC-3 (E2-insensitive) prostate cancer cell lines.
• Assessed cell proliferation, androgen receptor (AR) activity (luciferase reporter), and prostate-specific antigen (PSA) expression.
• Quantified gene expression of CYP1A1 and COMT using real-time RT-PCR.
• Measured estrogen metabolite levels using mass spectrometry (MS).

Main Results:

• DIM inhibited E2-induced proliferation in LNCaP cells; genistein showed dose-dependent effects.
• Genistein's proliferative effect was abolished by DIM.
• Both genistein and DIM abrogated E2-stimulated PSA expression and AR signaling.
• Genistein and DIM increased CYP1A1 and COMT expression, altering E2 metabolism towards less estrogenic forms.
• Combined genistein and DIM significantly increased COMT mRNA levels.

Conclusions:

• Genistein and DIM effectively counteract E2-driven proliferation and PSA expression in PCa cells.
• These phytochemicals modulate E2 metabolism by upregulating CYP1A1 and COMT, potentially reducing estrogenicity.
• DIM and genistein demonstrate significant potential in reducing E2-mediated risks associated with prostate cancer.