Antrocin Sensitizes Prostate Cancer Cells to Radiotherapy through Inhibiting PI3K/AKT and MAPK Signaling Pathways.
Yu-An ChenDavid T W TzengYi-Ping HuangChun-Jung LinU-Ging LoChia-Lin WuChung-Jung LinJer-Tsong HsiehChih-Hsin TangChih-Ho LaiPublished in: Cancers (2018)
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.
Keyphrases
- signaling pathway
- pi k akt
- induced apoptosis
- cell cycle arrest
- cell proliferation
- cell cycle
- epithelial mesenchymal transition
- endoplasmic reticulum stress
- early stage
- prostate cancer
- oxidative stress
- radiation induced
- radiation therapy
- locally advanced
- cell death
- mouse model
- squamous cell carcinoma
- lymph node metastasis
- rectal cancer
- cancer stem cells
- smoking cessation
- dna damage response