References
Alcaraz A, Hammerer P, Tubaro A, Schroder FH, Castro R (2009) Is there evidence of a relation-
ship between benign prostatic hyperplasia and prostate cancer? Findings of a literature review.
Eur Urol 55:864–873. https://doi.org/10.1016/j.eururo.2008.11.011
Anglin IE, Glassman DT, Kyprianou N (2002) Induction of prostate apoptosis by alpha1-
adrenoceptor antagonists: mechanistic significance of the quinazoline component. Prostate
Cancer Prostatic Dis 5:88–95. https://doi.org/10.1038/sj.pcan.4500561
Benning CM, Kyprianou N (2002) Quinazoline-derived alpha1-adrenoceptor antagonists induce
prostate cancer cell apoptosis via an alpha1-adrenoceptor-independent action. Cancer Res 62:
597–602
Bostwick DG, Cooner WH, Denis L, Jones GW, Scardino PT, Murphy GP (1992) The association
of benign prostatic hyperplasia and cancer of the prostate. Cancer 70:291–301. https://doi.org/
10.1002/1097-0142(19920701)70:1+<291::aid-cncr2820701317>3.0.co;2-4
Bylund DB et al (1994) International Union of Pharmacology nomenclature of adrenoceptors.
Pharmacol Rev 46:121–136
Demirci S, Hayal TB, Kiratli B, Sisli HB, Demirci S, Sahin F, Dogan A (2019) Design and
synthesis of phenylpiperazine derivatives as potent anticancer agents for prostate cancer.
Chem Biol Drug Des 94:1584–1595. https://doi.org/10.1111/cbdd.13575
Garrison JB, Shaw YJ, Chen CS, Kyprianou N (2007) Novel quinazoline-based compounds impair
prostate tumorigenesis by targeting tumor vascularity. Cancer Res 67:11344–11352. https://doi.
org/10.1158/0008-5472.CAN-07-1662
Gronberg H (2003) Prostate cancer epidemiology. Lancet 361:859–864. https://doi.org/10.1016/
S0140-6736(03)12713-4
Guo FJ, Sun J, Gao LL, Wang XY, Zhang Y, Qian SS, Zhu HL (2015) Discovery of
phenylpiperazine derivatives as IGF-1R inhibitor with potent antiproliferative properties
in vitro. Bioorg Med Chem Lett 25:1067–1071. https://doi.org/10.1016/j.bmcl.2015.01.011
Harris AM et al (2007) Effect of alpha1-adrenoceptor antagonist exposure on prostate cancer
incidence: an observational cohort study. J Urol 178:2176–2180. https://doi.org/10.1016/j.
juro.2007.06.043
Hori Y et al (2011) Naftopidil, a selective {alpha}1-adrenoceptor antagonist, suppresses human
prostate tumor growth by altering interactions between tumor cells and stroma. Cancer Prev Res
(Phila) 4:87–96. https://doi.org/10.1158/1940-6207.CAPR-10-0189
Ishii K, Sugimura Y (2015) Identification of a new pharmacological activity of the phenylpiperazine
derivative naftopidil: tubulin-binding drug J. Chem Biol 8:5–9. https://doi.org/10.1007/s12154-
014-0122-0
Ishii K et al (2018a) Additive naftopidil treatment synergizes docetaxel-induced apoptosis in human
prostate cancer cells. J Cancer Res Clin Oncol 144:89–98. https://doi.org/10.1007/s00432-017-
2536-x
Ishii K, Takahashi S, Sugimura Y, Watanabe M (2018b) Role of stromal paracrine signals in
proliferative diseases of the aging human prostate. J Clin Med 7. https://doi.org/10.3390/
jcm7040068
Iwamoto Y et al (2013) Oral naftopidil suppresses human renal-cell carcinoma by inducing G
(1) cell-cycle arrest in tumor and vascular endothelial cells. Cancer Prev Res (Phila) 6:1000–
1006. https://doi.org/10.1158/1940-6207.CAPR-13-0095
Iwamoto Y et al (2017) Combination treatment with naftopidil increases the efficacy of radiother-
apy in PC-3 human prostate cancer cells. J Cancer Res Clin Oncol 143:933–939. https://doi.org/
10.1007/s00432-017-2367-9
Kanda H, Ishii K, Ogura Y, Imamura T, Kanai M, Arima K, Sugimura Y (2008) Naftopidil, a
selective alpha-1 adrenoceptor antagonist, inhibits growth of human prostate cancer cells by G1
cell cycle arrest. Int J Cancer 122:444–451. https://doi.org/10.1002/ijc.23095
Kawabe K (2006) Latest frontiers in pharmacotherapy for benign prostatic hyperplasia. Yakugaku
Zasshi 126:199–206. https://doi.org/10.1248/yakushi.126.199
118
K. Ishii et al.