Ceramide Regulates Anti-Tumor Mechanisms of Erianin in Androgen-Sensitive and Castration-Resistant Prostate Cancers
| Autor: | Anthony S. Don, Shubiao Zhang, Xin Tracy Liu, Yang Zhao, Chanlu Xie, Felcia Lai, Long Hoa Chung, Yanfei Qi, I Gusti Md Gde Surya C Trapika, Jinbiao Chen, Collin Tran, George Q. Li, Qian Wang, Shaohui Cui, Jane R. Hanrahan |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Cancer Research
Ceramide autophagy Cell cycle checkpoint Androgen deprivation therapy chemistry.chemical_compound Prostate cancer Prostate medicine RC254-282 Original Research Ceramide synthase 5 business.industry apoptosis Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease Sphingolipid medicine.anatomical_structure Oncology chemistry Apoptosis cell cycle arrest Cancer research endoplasmic reticulum stress sphingolipid business |
| Zdroj: | Frontiers in Oncology, Vol 11 (2021) Frontiers in Oncology |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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