title: In vitro and in vivo growth inhibition of prostate cancer by the small molecule imiquimod.
abstract: Prostate cancer is the second leading cause of cancer death in men worldwide. In the present study, we examined in vitro and in vivo antitumor effect of the small molecule imiquimod, also known as a TLR7 agonist, against prostate cancer. Imiquimod inhibited the growth of mouse (TRAMP‑C2) and human (PC-3) prostate cancer cells. Treatment with imiquimod induced cell cycle arrest at the G2/M phase in TRMPA-C2 cells, confirmed by the changes of G2/M checkpoint regulators such as reduction of cyclin B1 expression and increase of phospho-CDC2 and p21 in TRAMP-C2 cells treated with imiquimod. Flow cytometry and western blot analysis revealed that imiquimod induced direct apoptosis in TRAMP-C2 cells via a mitochondrial‑dependent pathway. Intratumoral injection with imiquimod reduced significantly tumor growth and increased apoptotic cells in mice subcutaneously implanted with TRAMP-C2 cells. Our results indicate that imiquimod can be an alternative therapeutic for locally generated prostate cancer.
authors.affiliation: Department of Laboratory Animal Medicine, College of Veterinary Medicine, Seoul National University, Seoul 151‑742, Republic of Korea.
authors.forename: Ju-Hee
authors.initials: JH
authors.lastname: Han
authors.forename: Junglim
authors.initials: J
authors.lastname: Lee
authors.forename: Soo-Jin
authors.initials: SJ
authors.lastname: Jeon
authors.forename: Eun-Sun
authors.initials: ES
authors.lastname: Choi
authors.forename: Sung-Dae
authors.initials: SD
authors.lastname: Cho
authors.forename: Bo-Yeon
authors.initials: BY
authors.lastname: Kim
authors.forename: Dong-Jae
authors.initials: DJ
authors.lastname: Kim
authors.forename: Jae-Hak
authors.initials: JH
authors.lastname: Park
authors.forename: Jong-Hwan
authors.initials: JH
authors.lastname: Park
mesh_terms: D000634:Aminoquinolines / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D002738:Chloroquine / Q000494:pharmacology; D056744:Cyclin B1 / Q000378:metabolism; D006801:Humans; D000077271:Imiquimod; D015552:Injections, Intralesional; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051199:Toll-Like Receptor 7 / Q000037:antagonists & inhibitors; D023041:Xenograft Model Antitumor Assays
chemical_list: D000634:Aminoquinolines; D000970:Antineoplastic Agents; D056744:Cyclin B1; C495348:TLR7 protein, human; D051199:Toll-Like Receptor 7; D002738:Chloroquine; D000077271:Imiquimod