Ceramide Regulates Anti-Tumor Mechanisms of Erianin in Androgen-Sensitive and Castration-Resistant Prostate Cancers

I Gusti Md Gde Surya C Trapika1,2, Xin Tracy Liu1, Long Hoa Chung1

  • 1Centenary Institute of Cancer Medicine and Cell Biology, University of Sydney, Camperdown, NSW, Australia.

Frontiers in Oncology
|October 4, 2021
PubMed

Insights

Erianin, a plant compound, shows anti-cancer effects in prostate cancer cells. It triggers cell death in early-stage cancers and halts progression in resistant forms by affecting C16 ceramide levels.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Prostate cancer is a prevalent malignancy, with early stages dependent on androgens.
  • A significant percentage of prostate cancers develop resistance to androgen deprivation therapy, necessitating novel treatments.
  • Erianin, a bibenzyl compound from plants, has demonstrated potential anti-tumor properties.

Purpose of the Study:

  • To investigate the anti-tumor effects of erianin on both androgen-sensitive and castration-resistant prostate cancer cells.
  • To elucidate the distinct mechanisms underlying erianin's action in different prostate cancer subtypes.
  • To explore the role of C16 ceramide in mediating cellular responses to erianin.

Main Methods:

  • Treatment of androgen-sensitive and castration-resistant prostate cancer cell lines with erianin.
  • Analysis of apoptosis induction via endoplasmic reticulum stress and autophagy.
  • Investigation of cell cycle progression, specifically M phase arrest.
  • Measurement of C16 ceramide levels and the role of ceramide synthase 5.

Main Results:

  • Erianin induced apoptosis in androgen-sensitive prostate cancer cells through endoplasmic reticulum stress and autophagy.
  • Erianin caused M phase cell cycle arrest, not apoptosis, in castration-resistant prostate cancer cells.
  • Erianin elevated C16 ceramide levels in androgen-sensitive cells but not in castration-resistant cells.
  • Overexpression of ceramide synthase 5 restored erianin-induced apoptosis in castration-resistant cells.

Conclusions:

  • Erianin exhibits differential anti-tumor mechanisms in various prostate cancer types.
  • C16 ceramide plays a crucial role in determining cellular sensitivity to erianin.
  • Erianin represents a promising therapeutic candidate for prostate cancer treatment.

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