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Open AccessArticle

Antrocin Sensitizes Prostate Cancer Cells to Radiotherapy through Inhibiting PI3K/AKT and MAPK Signaling Pathways

1
Graduate Institute of Basic Medical Science, School of Medicine, China Medical University, Taichung 40402, Taiwan
2
Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
3
Department of Microbiology and Immunology, Department of Biochemistry, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan
4
School of Life Sciences, The Chinese University of Hong Kong, Hong Kong 999077, China
5
Department of Neurology, Chang Gung Memorial Hospital, Linkou 33305, Taiwan
6
Department of Life Sciences, National Chung Hsing University, Taichung 40227, Taiwan
7
Graduate Institute of Biomedical Sciences, China Medical University, Taichung 40202, Taiwan
8
Department of Nursing, Asia University, Taichung 41354, Taiwan
9
Molecular Infectious Disease Research Center, Department of Pediatrics, Chang Gung Memorial Hospital, Linkou 33305, Taiwan
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Cancers 2019, 11(1), 34; https://doi.org/10.3390/cancers11010034
Received: 29 October 2018 / Revised: 20 December 2018 / Accepted: 25 December 2018 / Published: 31 December 2018
(This article belongs to the Special Issue New Developments in Radiotherapy)
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. View Full-Text
Keywords: prostate cancer; radiotherapy; radioresistance; antrocin prostate cancer; radiotherapy; radioresistance; antrocin
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Chen, Y.-A.; Tzeng, D.T.W.; Huang, Y.-P.; Lin, C.-J.; Lo, U.-G.; Wu, C.-L.; Lin, H.; Hsieh, J.-T.; Tang, C.-H.; Lai, C.-H. Antrocin Sensitizes Prostate Cancer Cells to Radiotherapy through Inhibiting PI3K/AKT and MAPK Signaling Pathways. Cancers 2019, 11, 34.

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