Raltitrexed induces apoptosis through activating ROS-mediated ER stress by impeding HSPA8 expression in prostate cancer cells
Copyright © 2024. Published by Elsevier B.V..
Prostate cancer is the most common malignant tumor in males, which frequently develops into castration-resistant prostate cancer (CRPC). CRPC metastasis is the main reason for its high mortality rate. At present, it lacks effective treatment for patients with CRPC. Raltitrexed (RTX) has been shown to be effective in the treatment of colorectal cancer. However, the effect of RTX on prostate cancer and the underlying mechanism remain unknown. In the current study, we found that RTX could dose-dependently inhibit proliferation, migration, colony formation and induce apoptosis in DU145 and PC-3 cells. RTX also increased ROS generation in prostate cancer cells. Pretreatment with N-acetyl-L-cysteine (NAC) significantly prevented RTX-induced cell apoptosis and endoplasmic reticulum (ER) stress signaling activation in prostate cancer cells. Additionally, we found RTX-induced ROS generation and ER stress activation depended on the expression of heat shock protein family A member 8 (HSPA8). Over-expression of HSPA8 could alleviate RTX-induced cell apoptosis, ROS generation and ER stress signaling activation. Finally, our study also showed that RTX attenuated the tumor growth of prostate cancer in the DU145 xenograft model and significantly downregulated HSPA8 expression and activated ER stress signaling pathway in tumor tissues. Our study is the first to reveal that RTX induces prostate cancer cells apoptosis through inhibiting the expression of HSPA8 and further inducing ROS-mediated ER stress pathway action. This study suggests that RTX may be a novel promising candidate drug for prostate cancer therapy.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:1871 |
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| Enthalten in: |
Biochimica et biophysica acta. Molecular cell research - 1871(2024), 3 vom: 30. März, Seite 119684 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Tao, Yan [VerfasserIn] |
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| Links: |
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| Themen: |
Apoptosis |
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| Anmerkungen: |
Date Completed 04.03.2024 Date Revised 04.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.bbamcr.2024.119684 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
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| 520 | |a Copyright © 2024. Published by Elsevier B.V. | ||
| 520 | |a Prostate cancer is the most common malignant tumor in males, which frequently develops into castration-resistant prostate cancer (CRPC). CRPC metastasis is the main reason for its high mortality rate. At present, it lacks effective treatment for patients with CRPC. Raltitrexed (RTX) has been shown to be effective in the treatment of colorectal cancer. However, the effect of RTX on prostate cancer and the underlying mechanism remain unknown. In the current study, we found that RTX could dose-dependently inhibit proliferation, migration, colony formation and induce apoptosis in DU145 and PC-3 cells. RTX also increased ROS generation in prostate cancer cells. Pretreatment with N-acetyl-L-cysteine (NAC) significantly prevented RTX-induced cell apoptosis and endoplasmic reticulum (ER) stress signaling activation in prostate cancer cells. Additionally, we found RTX-induced ROS generation and ER stress activation depended on the expression of heat shock protein family A member 8 (HSPA8). Over-expression of HSPA8 could alleviate RTX-induced cell apoptosis, ROS generation and ER stress signaling activation. Finally, our study also showed that RTX attenuated the tumor growth of prostate cancer in the DU145 xenograft model and significantly downregulated HSPA8 expression and activated ER stress signaling pathway in tumor tissues. Our study is the first to reveal that RTX induces prostate cancer cells apoptosis through inhibiting the expression of HSPA8 and further inducing ROS-mediated ER stress pathway action. This study suggests that RTX may be a novel promising candidate drug for prostate cancer therapy | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Apoptosis | |
| 650 | 4 | |a ER stress | |
| 650 | 4 | |a HSPA8 | |
| 650 | 4 | |a Prostate cancer | |
| 650 | 4 | |a Raltitrexed | |
| 650 | 4 | |a Reactive oxygen species | |
| 650 | 7 | |a Reactive Oxygen Species |2 NLM | |
| 650 | 7 | |a raltitrexed |2 NLM | |
| 650 | 7 | |a FCB9EGG971 |2 NLM | |
| 650 | 7 | |a HSPA8 protein, human |2 NLM | |
| 650 | 7 | |a HSC70 Heat-Shock Proteins |2 NLM | |
| 650 | 7 | |a Quinazolines |2 NLM | |
| 650 | 7 | |a Thiophenes |2 NLM | |
| 700 | 1 | |a Lu, Jianzhong |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Lanlan |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Lanpeng |e verfasserin |4 aut | |
| 700 | 1 | |a Fu, Beitang |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Jing |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Shuni |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Ruicong |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Jialong |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Jiaping |e verfasserin |4 aut | |
| 700 | 1 | |a Fu, Shengjun |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Shanhui |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Zhiping |e verfasserin |4 aut | |
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