Frontiers in Oncology (Sep 2021)

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

  • I Gusti Md Gde Surya C. Trapika,
  • I Gusti Md Gde Surya C. Trapika,
  • Xin Tracy Liu,
  • Long Hoa Chung,
  • Felcia Lai,
  • Felcia Lai,
  • Chanlu Xie,
  • Chanlu Xie,
  • Yang Zhao,
  • Shaohui Cui,
  • Jinbiao Chen,
  • Collin Tran,
  • Qian Wang,
  • Shubiao Zhang,
  • Anthony S. Don,
  • Anthony S. Don,
  • George Qian Li,
  • Jane R. Hanrahan,
  • Yanfei Qi

DOI
https://doi.org/10.3389/fonc.2021.738078
Journal volume & issue
Vol. 11

Abstract

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Prostate cancer is the second most prevalent malignancy worldwide. In the early stages, the development of prostate cancer is dependent on androgens. Over time with androgen deprivation therapy, 20% of prostate cancers progress to a castration-resistant form. Novel treatments for prostate cancers are still urgently needed. Erianin is a plant-derived bibenzyl compound. We report herein that erianin exhibits anti-tumor effects in androgen-sensitive and castration-resistant prostate cancer cells through different mechanisms. Erianin induces endoplasmic reticulum stress-associated apoptosis in androgen-sensitive prostate cancer cells. It also triggers pro-survival autophagic responses, as inhibition of autophagy predisposes to apoptosis. In contrast, erianin fails to induce apoptosis in castration-resistant prostate cancer cells. Instead, it results in cell cycle arrest at the M phase. Mechanistically, C16 ceramide dictates differential responses of androgen-sensitive and castration-resistant prostate cancer cells to erianin. Erianin elevates C16 ceramide level in androgen-sensitive but not castration-resistant prostate cancer cells. Overexpression of ceramide synthase 5 that specifically produces C16 ceramide enables erianin to induce apoptosis in castration-resistant prostate cancer cells. Our study provides both experimental evidence and mechanistic data showing that erianin is a potential treatment option for prostate cancers.

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