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Sequencing Small Non-coding RNA from Formalin-fixed Tissues and Serum-derived Exosomes from Castration-resistant Prostate Cancer Patients
Published on: November 19, 2019
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.
Abstract:
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.
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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