HASPIN kinase inhibitor CHR-6494 suppresses intestinal polyp development, cachexia, and hypogonadism in Apcmin/+ mice. Issue 6 (November 2020)

• Record Type: Journal Article
• Authors: Tanaka, Hiromitsu; Wada, Morimasa; Park, Junhyeok
• Is Part Of: European journal of cancer prevention. Volume 29:Issue 6(2020)
• Publication Date: 2020-11
• Subjects: cancer -- chemoprevention -- infertility -- testis -- testosterone; Cancer -- Prevention -- Periodicals; Neoplasms -- etiology -- Periodicals; Neoplasms -- prevention & control -- Periodicals; Cancer -- Prevention; Periodicals; 616.994052
• DOI: 10.1097/CEJ.0000000000000562
• Languages: English
• ISSNs: 0959-8278

Abstract

Abstract : HASPIN has been identified as a nuclear Ser/Thr kinase specifically expressed in haploid germ cells. HASPIN kinase inhibitors were recently isolated, and their antitumor activity reported. Colorectal cancer occurs with high incidence worldwide. In this study, we examined whether HASPIN inhibitor CHR-6494 suppresses cancer progression in Apc Min/+ mice, a familial colon tumor disease model. Mice were treated by intraperitoneal injection of CHR-6494 for 50 days. Following the treatment period, intestinal polyps were counted and testosterone and spermatogenesis levels were observed. Intraperitoneal administration of CHR-6494 significantly inhibited intestinal polyp development and recovered body weight in Apc Min/+ mice. Although spermatogenesis was inhibited with increasing age in Apc Min /+ mice, CHR-6494 significantly improved blood testosterone levels and spermatogenesis. Our results suggest that HASPIN inhibitors may be useful as anti-cancer agents and for the treatment of hypogonadism in colorectal cancer patients.