Biomolecules & Therapeutics

  • 제28권2호
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  • Pages.195-201
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  • 2020
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  • 1976-9148(pISSN)
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  • 2005-4483(eISSN)
한국응용약물학회 (The Korean Society of Applied Pharmacology)
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Functional Expression of Choline Transporter-Like Protein 1 in LNCaP Prostate Cancer Cells: A Novel Molecular Target

  • Saiki, Iwao (Department of Anesthesiology, Tokyo Medical University) ;
  • Yara, Miki (Department of Anesthesiology, Tokyo Medical University) ;
  • Yamanaka, Tsuyoshi (Department of Molecular Preventive Medicine, Tokyo Medical University) ;
  • Uchino, Hiroyuki (Department of Anesthesiology, Tokyo Medical University) ;
  • Inazu, Masato (Department of Molecular Preventive Medicine, Tokyo Medical University)
  • 투고 : 2019.06.12
  • 심사 : 2019.10.01
  • 발행 : 2020.03.01
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초록

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.

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참고문헌

  1. Anderson, O. S., Sant, K. E. and Dolinoy, D. C. (2012) Nutrition and epigenetics: an interplay of dietary methyl donors, one-carbon metabolism, and DNA methylation. J. Nutr. Biochem. 23, 853-859. https://doi.org/10.1016/j.jnutbio.2012.03.003
  2. Cheng, Y. and Prusoff, W. H. (1973) Relationship between the inhibition constant (Ki) and the concentration of inhibitor which causes 50 percent inhibition (IC50) of an enzymatic reaction. Biochem. Pharmacol. 22, 3099-3108. https://doi.org/10.1016/0006-2952(73)90196-2
  3. Choong, C. S. and Wilson, E. M. (1998) Trinucleotide repeats in the human androgen receptor: a molecular basis for disease. J. Mol. Endocrinol. 21, 235-257. https://doi.org/10.1677/jme.0.0210235
  4. Crawford, E. D., Schellhammer, P. F., McLeod, D. G., Moul, J. W., Higano, C. S., Shore, N., Denis, L., Iversen, P., Eisenberger, M. A. and Labrie, F. (2018) Androgen receptor targeted treatments of prostate cancer: 35 years of progress with antiandrogens. J. Urol. 200, 956-966. https://doi.org/10.1016/j.juro.2018.04.083
  5. Hara, T., Inagaki, K., Kosaka, N. and Morita, T. (2000) Sensitive detection of mediastinal lymph node metastasis of lung cancer with 11C-choline PET. J. Nucl. Med. 41, 1507-1513.
  6. Hara, T., Kosaka, N. and Kishi, H. (1998) PET imaging of prostate cancer using carbon-11-choline. J. Nucl. Med. 39, 990-995.
  7. Inazu, M. (2014) Choline transporter-like proteins CTLs/SLC44 family as a novel molecular target for cancer therapy. Biopharm. Drug Dispos. 35, 431-449. https://doi.org/10.1002/bdd.1892
  8. Inazu, M., Takeda, H. and Matsumiya, T. (2005) Molecular and functional characterization of an $Na^+$-independent choline transporter in rat astrocytes. J. Neurochem. 94, 1427-1437. https://doi.org/10.1111/j.1471-4159.2005.03299.x
  9. Inazu, M., Yamada, T., Kubota, N. and Yamanaka, T. (2013) Functional expression of choline transporter-like protein 1 (CTL1) in small cell lung carcinoma cells: a target molecule for lung cancer therapy. Pharmacol. Res. 76, 119-131. https://doi.org/10.1016/j.phrs.2013.07.011
  10. Kaplan, C. P., Porter, R. K. and Brand, M. D. (1993) The choline transporter is the major site of control of choline oxidation in isolated rat liver mitochondria. FEBS Lett. 321, 24-26. https://doi.org/10.1016/0014-5793(93)80613-Y
  11. Kobori, O., Kirihara, Y., Kosaka, N. and Hara, T. (1999) Positron emission tomography of esophageal carcinoma using (11)C-choline and (18)F-fluorodeoxyglucose: a novel method of preoperative lymph node staging. Cancer 86, 1638-1648. https://doi.org/10.1002/(SICI)1097-0142(19991101)86:9<1638::AID-CNCR4>3.0.CO;2-U
  12. Kotzerke, J., Prang, J., Neumaier, B., Volkmer, B., Guhlmann, A., Kleinschmidt, K., Hautmann, R. and Reske, S. N. (2000) Experience with carbon-11 choline positron emission tomography in prostate carcinoma. Eur. J. Nucl. Med. 27, 1415-1419. https://doi.org/10.1007/s002590000309
  13. Michel, V. and Bakovic, M. (2012) The ubiquitous choline transporter SLC44A1. Cent. Nerv. Syst. Agents Med. Chem. 12, 70-81. https://doi.org/10.2174/187152412800792733
  14. Michel, V., Yuan, Z., Ramsubir, S. and Bakovic, M. (2006) Choline transport for phospholipid synthesis. Exp. Biol. Med. (Maywood) 231, 490-504. https://doi.org/10.1177/153537020623100503
  15. Muller, S. A., Holzapfel, K., Seidl, C., Treiber, U., Krause, B. J. and Senekowitsch-Schmidtke, R. (2009) Characterization of choline uptake in prostate cancer cells following bicalutamide and docetaxel treatment. Eur. J. Nucl. Med. Mol. Imaging 36, 1434-1442. https://doi.org/10.1007/s00259-009-1117-x
  16. Nabokina, S. M., Inoue, K., Subramanian, V. S., Valle, J. E., Yuasa, H. and Said, H. M. (2014) Molecular identification and functional characterization of the human colonic thiamine pyrophosphate transporter. J. Biol. Chem. 289, 4405-4416. https://doi.org/10.1074/jbc.M113.528257
  17. Nagashima, F., Nishiyama, R., Iwao, B., Kawai, Y., Ishii, C., Yamanaka, T., Uchino, H. and Inazu, M. (2018) Molecular and functional characterization of choline transporter-like proteins in esophageal cancer cells and potential therapeutic targets. Biomol. Ther. (Seoul) 26, 399-408. https://doi.org/10.4062/biomolther.2017.113
  18. Nishiyama, R., Nagashima, F., Iwao, B., Kawai, Y., Inoue, K., Midori, A., Yamanaka, T., Uchino, H. and Inazu, M. (2016) Identification and functional analysis of choline transporter in tongue cancer: a novel molecular target for tongue cancer therapy. J. Pharmacol. Sci. 131, 101-109. https://doi.org/10.1016/j.jphs.2016.04.022
  19. O'Donoghue, N., Sweeney, T., Donagh, R., Clarke, K. J. and Porter, R. K. (2009) Control of choline oxidation in rat kidney mitochondria. Biochim. Biophys. Acta 1787, 1135-1139. https://doi.org/10.1016/j.bbabio.2009.04.014
  20. Ohtani, T., Kurihara, H., Ishiuchi, S., Saito, N., Oriuchi, N., Inoue, T. and Sasaki, T. (2001) Brain tumour imaging with carbon-11 choline: comparison with FDG PET and gadolinium-enhanced MR imaging. Eur. J. Nucl. Med. 28, 1664-1670. https://doi.org/10.1007/s002590100620
  21. Porter, R. K., Scott, J. M. and Brand, M. D. (1992) Choline transport into rat liver mitochondria. Characterization and kinetics of a specific transporter. J. Biol. Chem. 267, 14637-14646. https://doi.org/10.1016/S0021-9258(18)42089-3
  22. Reske, S. N., Blumstein, N. M., Neumaier, B., Gottfried, H. W., Finsterbusch, F., Kocot, D., Moller, P., Glatting, G. and Perner, S. (2006) Imaging prostate cancer with 11C-choline PET/CT. J. Nucl. Med. 47, 1249-1254.
  23. Rinnab, L., Blumstein, N. M., Mottaghy, F. M., Hautmann, R. E., Kufer, R., Hohl, K. and Reske, S. N. (2007) 11C-choline positron-emission tomography/computed tomography and transrectal ultrasonography for staging localized prostate cancer. BJU Int. 99, 1421-1426. https://doi.org/10.1111/j.1464-410X.2007.06776.x
  24. Schwarzenbock, S., Souvatzoglou, M. and Krause, B. J. (2012) Choline PET and PET/CT in primary diagnosis and staging of prostate cancer. Theranostics 2, 318-330. https://doi.org/10.7150/thno.4008
  25. Taguchi, C., Inazu, M., Saiki, I., Yara, M., Hara, N., Yamanaka, T. and Uchino, H. (2014) Functional analysis of [methyl-(3)H]choline uptake in glioblastoma cells: influence of anti-cancer and central nervous system drugs. Biochem. Pharmacol. 88, 303-312. https://doi.org/10.1016/j.bcp.2014.01.033
  26. Tian, M., Zhang, H., Oriuchi, N., Higuchi, T. and Endo, K. (2004) Comparison of 11C-choline PET and FDG PET for the differential diagnosis of malignant tumors. Eur. J. Nucl. Med. Mol. Imaging 31, 1064-1072. https://doi.org/10.1007/s00259-004-1496-y
  27. van Asten, J. J, Cuijpers, V., Hulsbergen-van de Kaa, C., Soede-Huijbregts, C., Witjes, J. A., Verhofstad, A. and Heerschap, A. (2008) High resolution magic angle spinning NMR spectroscopy for metabolic assessment of cancer presence and Gleason score in human prostate needle biopsies. MAGMA 21, 435-442. https://doi.org/10.1007/s10334-008-0156-9
  28. Xu, K. M., Chen, R. C., Schuster, D. M. and Jani, A. B. (2019) Role of novel imaging in the management of prostate cancer. Urol. Oncol. 37, 611-618. https://doi.org/10.1016/j.urolonc.2019.04.008
  29. Yamada, T., Inazu, M., Tajima, H. and Matsumiya, T. (2011) Functional expression of choline transporter-like protein 1 (CTL1) in human neuroblastoma cells and its link to acetylcholine synthesis. Neurochem. Int. 58, 354-365. https://doi.org/10.1016/j.neuint.2010.12.011

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