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Int J Mol Sci. 2019 Apr 3;20(7). pii: E1647. doi: 10.3390/ijms20071647.

AICAR Induces Apoptosis and Inhibits Migration and Invasion in Prostate Cancer Cells Through an AMPK/mTOR-Dependent Pathway.

Su CC1,2,3, Hsieh KL4, Liu PL5, Yeh HC6,7,8, Huang SP9,10, Fang SH11, Cheng WC12, Huang KH13, Chiu FY14, Lin IL15, Huang MY16,17,18, Li CY19,20.

Author information

1
Division of Urology, Department of Surgery, Chi-Mei Medical Center, Tainan 71004, Taiwan. s2341438@yahoo.com.tw.
2
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. s2341438@yahoo.com.tw.
3
Department of Senior Citizen Service Management, Chia Nan University of Pharmacy and Science, Tainan 71710, Taiwan. s2341438@yahoo.com.tw.
4
Division of Urology, Department of Surgery, Chi-Mei Medical Center, Tainan 71004, Taiwan. samlin.hsieh@gmail.com.
5
Department of Respiratory Therapy, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. kisa@kmu.edu.tw.
6
Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. patrick1201.tw@yahoo.com.tw.
7
Department of Urology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung 80145, Taiwan. patrick1201.tw@yahoo.com.tw.
8
Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. patrick1201.tw@yahoo.com.tw.
9
Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. shpihu73@gmail.com.
10
Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. shpihu73@gmail.com.
11
Institute of Athletics, National Taiwan University of Sport, Taichung 40404, Taiwan. shfang@ntupes.edu.tw.
12
Graduate Institute of Biomedical Sciences, and Research Center for Tumor Medical Science, China Medical University, Taichung 40402, Taiwan. cwc0702@gmail.com.
13
Division of Urology, Department of Surgery, Chi-Mei Medical Center, Tainan 71004, Taiwan. skhsteven@gmail.com.
14
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. fangyen0210@hotmail.com.
15
Department of Medical Laboratory Science and Biotechnology, College of Health Sciences, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. linili@kmu.edu.tw.
16
Department of Radiation Oncology, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan. miyihu@gmail.com.
17
Department of Radiation Oncology, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. miyihu@gmail.com.
18
Center for Biomarkers and Biotech Drugs, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. miyihu@gmail.com.
19
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. chiayangli@kmu.edu.tw.
20
Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. chiayangli@kmu.edu.tw.

Abstract

Current clinical challenges of prostate cancer management are to restrict tumor growth and prohibit metastasis. AICAR (5-aminoimidazole-4-carbox-amide-1-β-d-ribofuranoside), an AMP-activated protein kinase (AMPK) agonist, has demonstrated antitumor activities for several types of cancers. However, the activity of AICAR on the cell growth and metastasis of prostate cancer has not been extensively studied. Herein we examine the effects of AICAR on the cell growth and metastasis of prostate cancer cells. Cell growth was performed by MTT assay and soft agar assay; cell apoptosis was examined by Annexin V/propidium iodide (PI) staining and poly ADP ribose polymerase (PARP) cleavage western blot, while cell migration and invasion were evaluated by wound-healing assay and transwell assay respectively. Epithelial-mesenchymal transition (EMT)-related protein expression and AMPK/mTOR-dependent signaling axis were analyzed by western blot. In addition, we also tested the effect of AICAR on the chemosensitivity to docetaxel using MTT assay. Our results indicated that AICAR inhibits cell growth in prostate cancer cells, but not in non-cancerous prostate cells. In addition, our results demonstrated that AICAR induces apoptosis, attenuates transforming growth factor (TGF)-β-induced cell migration, invasion and EMT-related protein expression, and enhances the chemosensitivity to docetaxel in prostate cancer cells through regulating the AMPK/mTOR-dependent pathway. These findings support AICAR as a potential therapeutic agent for the treatment of prostate cancer.

KEYWORDS:

AICAR; AMPK; chemosensitivity; metastasis; prostate cancer

PMID:
30987073
PMCID:
PMC6480054
DOI:
10.3390/ijms20071647
[Indexed for MEDLINE]
Free PMC Article

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