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Published on: September 18, 2013

Pomegranate extract induces apoptosis in human prostate cancer cells by modulation of the IGF-IGFBP axis

Satomi Koyama1, Laura J Cobb, Hemal H Mehta

  • 1Division of Pediatric Endocrinology, Mattel Children's Hospital, David Geffen School of Medicine, University of California, Los Angeles, USA.

Growth Hormone & IGF Research : Official Journal of the Growth Hormone Research Society and the International IGF Research Society
|October 27, 2009
PubMed

Insights

Pomegranate extract (POMx) induces apoptosis in prostate cancer cells by modulating the insulin-like growth factor (IGF) system. Co-treatment with IGFBP-3 enhances this effect, while IGF-1 blocks it, highlighting POMx

Area of Science:

  • Oncology
  • Molecular Biology
  • Nutritional Science

Background:

  • The insulin-like growth factor (IGF) axis plays a crucial role in regulating apoptosis in human cancer cells.
  • Pomegranate juice and extracts exhibit potent anti-tumorigenic effects, suggesting potential in cancer prevention and treatment, particularly for prostate cancer.
  • Understanding the interaction between pomegranate's anti-cancer properties and the IGF system is key to elucidating its therapeutic mechanisms.

Purpose of the Study:

  • To investigate the relationship between pomegranate extract-induced apoptosis in human prostate cancer cells and the IGF/IGF binding protein (IGFBP) system.
  • To explore the synergistic or antagonistic effects of pomegranate extract (POMx) in combination with IGFBP-3 and IGF-1 on prostate cancer cell growth and apoptosis.
  • To determine the impact of POMx on IGF-1 expression and the role of the IGF-1 receptor (IGF-IR) in mediating pomegranate's effects.

Main Methods:

  • Treatment of LAPC4 and 22RV1 prostate cancer cells with POMx, a standardized pomegranate extract.
  • Co-treatment experiments involving POMx with IGFBP-3 and IGF-1.
  • Western blot analysis to assess JNK phosphorylation, Akt, and mTOR activation.
  • Investigation of IGF-1 mRNA expression and the effect of IGF-1 on POMx-induced apoptosis in different cell lines (R(-) cells).

Main Results:

  • POMx treatment inhibited cell proliferation and induced apoptosis in LAPC4 prostate cancer cells.
  • Co-treatment with POMx and IGFBP-3 synergistically stimulated apoptosis and additively inhibited cell growth.
  • POMx treatment increased JNK phosphorylation and decreased Akt and mTOR activation.
  • IGF-1 completely blocked POMx-induced apoptosis in 22RV1 cells, whereas it failed to inhibit it in R(-) cells, indicating IGF-IR importance.
  • POMx treatment dose-dependently decreased Igf1 mRNA expression, suggesting tumor-specific suppression of IGF-1.

Conclusions:

  • Pomegranate extract (POMx) exhibits anti-proliferative and pro-apoptotic effects on prostate cancer cells.
  • The IGF/IGFBP system significantly modulates the apoptotic response to POMx, with IGFBP-3 enhancing and IGF-1 inhibiting the effect.
  • POMx exerts its effects partly through modulation of signaling pathways (JNK, Akt, mTOR) and suppression of tumor-specific IGF-1 expression.
  • These findings reveal novel interactions between the IGF system and pomegranate-induced apoptosis, supporting pomegranate's potential as a therapeutic or preventative agent for prostate cancer.

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