Functional Expression of Choline Transporter-Like Protein 1 in LNCaP Prostate Cancer Cells: A Novel Molecular Target
Iwao Saiki1, Miki Yara1, Tsuyoshi Yamanaka2, Hiroyuki Uchino1 and Masato Inazu2,3,*
1Department of Anesthesiology, Tokyo Medical University, Tokyo 160-0023,
2Department of Molecular Preventive Medicine, Tokyo Medical University, Tokyo 160-8402,
3Institute of Medical Science, Tokyo Medical University, Tokyo 160-8402, Japan
*E-mail: inazu@tokyo-med.ac.jp
Tel: +81-3-3351-6141, Fax: +81-3-3351-6166
Received: June 12, 2019; Revised: September 12, 2019; Accepted: October 1, 2019; Published online: November 6, 2019.
© The Korean Society of Applied Pharmacology. All rights reserved.

Abstract
Prostate cancer is one of the most common cancers in men. Choline PET or PET/CT has been used to visualize prostate cancer, and high levels of choline accumulation have been observed in tumors. However, the uptake system for choline and the functional expression of choline transporters in prostate cancer are not completely understood. In this study, the molecular and functional aspects of choline uptake were investigated in the LNCaP prostate cancer cell line along with the correlations between choline uptake and cell viability in drug-treated cells. Choline transporter-like protein 1 (CTL1) and CTL2 mRNA were highly expressed in LNCaP cells. CTL1 and CTL2 were located in the plasma membrane and mitochondria, respectively. [3H]Choline uptake was mediated by a single Na+-independent, intermediate-affinity transport system in the LNCaP cells. The anticancer drugs, flutamide and bicalutamide, inhibited cell viability and [3H]choline uptake in a concentration-dependent manner. The correlations between the effects of these drugs on cell viability and [3H]choline uptake were significant. Caspase-3/7 activity was significantly increased by both flutamide and bicalutamide. Furthermore, these drugs decreased CTL1 expression in the prostate cancer cell line. These results suggest that CTL1 is functionally expressed in prostate cancer cells and are also involved in abnormal proliferation. Identification of this CTL1-mediated choline transport system in prostate cancer cells provides a potential new therapeutic target for the treatment of this disease.
Keywords: Choline, Transporter, Prostate cancer, Apoptotic cell death, Caspase


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