Antrocin Sensitizes Prostate Cancer Cells to Radiotherapy through Inhibiting PI3K/AKT and MAPK Signaling Pathways
Radiotherapy is one of the most common treatment options for local or regional advanced prostate cancer (PCa). Importantly, PCa is prone to radioresistance and often develops into malignancies after long-term radiotherapy. Antrocin, a sesquiterpene lactone isolated from Antrodia cinnamomea, possesse...
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| Format: | Article |
| Language: | English |
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MDPI AG
2018-12-01
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| Series: | Cancers |
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| Online Access: | http://www.mdpi.com/2072-6694/11/1/34 |
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| author | Yu-An Chen David T. W. Tzeng Yi-Ping Huang Chun-Jung Lin U-Ging Lo Chia-Lin Wu Ho Lin Jer-Tsong Hsieh Chih-Hsin Tang Chih-Ho Lai |
| author_facet | Yu-An Chen David T. W. Tzeng Yi-Ping Huang Chun-Jung Lin U-Ging Lo Chia-Lin Wu Ho Lin Jer-Tsong Hsieh Chih-Hsin Tang Chih-Ho Lai |
| author_sort | Yu-An Chen |
| collection | DOAJ |
| description | Radiotherapy is one of the most common treatment options for local or regional advanced prostate cancer (PCa). Importantly, PCa is prone to radioresistance and often develops into malignancies after long-term radiotherapy. Antrocin, a sesquiterpene lactone isolated from Antrodia cinnamomea, possesses pharmacological efficacy against various cancer types; however, its therapeutic potential requires comprehensive exploration, particularly in radioresistant PCa cells. In this study, we emphasized the effects of antrocin on radioresistant PCa cells and addressed the molecular mechanism underlying the radiosensitization induced by antrocin. Our results showed that a combination treatment with antrocin and ionizing radiation (IR) synergistically inhibited cell proliferation and induced apoptosis in radioresistant PCa cells. We further demonstrated that antrocin downregulated PI3K/AKT and MAPK signaling pathways as well as suppressed type 1 insulin-like growth factor 1 receptor (IGF-1R)-mediated induction of β-catenin to regulate cell cycle and apoptosis. Using xenograft mouse models, we showed that antrocin effectively enhanced radiotherapy in PCa. Our study demonstrates that antrocin sensitizes PCa to radiation through constitutive suppression of IGF-1R downstream signaling, revealing that it can be developed as a potent therapeutic agent to overcome radioresistant PCa. |
| first_indexed | 2024-03-12T18:27:55Z |
| format | Article |
| id | doaj.art-4cef60f109984f8b9708c378aa0d72c2 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-12T18:27:55Z |
| publishDate | 2018-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-4cef60f109984f8b9708c378aa0d72c22023-08-02T08:27:47ZengMDPI AGCancers2072-66942018-12-011113410.3390/cancers11010034cancers11010034Antrocin Sensitizes Prostate Cancer Cells to Radiotherapy through Inhibiting PI3K/AKT and MAPK Signaling PathwaysYu-An Chen0David T. W. Tzeng1Yi-Ping Huang2Chun-Jung Lin3U-Ging Lo4Chia-Lin Wu5Ho Lin6Jer-Tsong Hsieh7Chih-Hsin Tang8Chih-Ho Lai9Graduate Institute of Basic Medical Science, School of Medicine, China Medical University, Taichung 40402, TaiwanSchool of Life Sciences, The Chinese University of Hong Kong, Hong Kong 999077, ChinaGraduate Institute of Basic Medical Science, School of Medicine, China Medical University, Taichung 40402, TaiwanDepartment of Urology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USADepartment of Urology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USADepartment of Microbiology and Immunology, Department of Biochemistry, College of Medicine, Chang Gung University, Taoyuan 33302, TaiwanDepartment of Life Sciences, National Chung Hsing University, Taichung 40227, TaiwanDepartment of Urology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USAGraduate Institute of Basic Medical Science, School of Medicine, China Medical University, Taichung 40402, TaiwanGraduate Institute of Basic Medical Science, School of Medicine, China Medical University, Taichung 40402, TaiwanRadiotherapy is one of the most common treatment options for local or regional advanced prostate cancer (PCa). Importantly, PCa is prone to radioresistance and often develops into malignancies after long-term radiotherapy. Antrocin, a sesquiterpene lactone isolated from Antrodia cinnamomea, possesses pharmacological efficacy against various cancer types; however, its therapeutic potential requires comprehensive exploration, particularly in radioresistant PCa cells. In this study, we emphasized the effects of antrocin on radioresistant PCa cells and addressed the molecular mechanism underlying the radiosensitization induced by antrocin. Our results showed that a combination treatment with antrocin and ionizing radiation (IR) synergistically inhibited cell proliferation and induced apoptosis in radioresistant PCa cells. We further demonstrated that antrocin downregulated PI3K/AKT and MAPK signaling pathways as well as suppressed type 1 insulin-like growth factor 1 receptor (IGF-1R)-mediated induction of β-catenin to regulate cell cycle and apoptosis. Using xenograft mouse models, we showed that antrocin effectively enhanced radiotherapy in PCa. Our study demonstrates that antrocin sensitizes PCa to radiation through constitutive suppression of IGF-1R downstream signaling, revealing that it can be developed as a potent therapeutic agent to overcome radioresistant PCa.http://www.mdpi.com/2072-6694/11/1/34prostate cancerradiotherapyradioresistanceantrocin |
| spellingShingle | Yu-An Chen David T. W. Tzeng Yi-Ping Huang Chun-Jung Lin U-Ging Lo Chia-Lin Wu Ho Lin Jer-Tsong Hsieh Chih-Hsin Tang Chih-Ho Lai Antrocin Sensitizes Prostate Cancer Cells to Radiotherapy through Inhibiting PI3K/AKT and MAPK Signaling Pathways Cancers prostate cancer radiotherapy radioresistance antrocin |
| title | Antrocin Sensitizes Prostate Cancer Cells to Radiotherapy through Inhibiting PI3K/AKT and MAPK Signaling Pathways |
| title_full | Antrocin Sensitizes Prostate Cancer Cells to Radiotherapy through Inhibiting PI3K/AKT and MAPK Signaling Pathways |
| title_fullStr | Antrocin Sensitizes Prostate Cancer Cells to Radiotherapy through Inhibiting PI3K/AKT and MAPK Signaling Pathways |
| title_full_unstemmed | Antrocin Sensitizes Prostate Cancer Cells to Radiotherapy through Inhibiting PI3K/AKT and MAPK Signaling Pathways |
| title_short | Antrocin Sensitizes Prostate Cancer Cells to Radiotherapy through Inhibiting PI3K/AKT and MAPK Signaling Pathways |
| title_sort | antrocin sensitizes prostate cancer cells to radiotherapy through inhibiting pi3k akt and mapk signaling pathways |
| topic | prostate cancer radiotherapy radioresistance antrocin |
| url | http://www.mdpi.com/2072-6694/11/1/34 |
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