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Published on: October 6, 2014
HASPIN kinase inhibitor CHR-6494 suppresses intestinal polyp development, cachexia, and hypogonadism in Apcmin/+ mice
Hiromitsu Tanaka1, Morimasa Wada, Junhyeok Park
1Faculty of Pharmaceutical Sciences, Nagasaki International University, Sasebo, Nagasaki, Japan.
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 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 mice. Although spermatogenesis was inhibited with increasing age in Apc 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.
Insights
HASPIN inhibitor CHR-6494 suppressed colorectal cancer progression in Apc mice. The treatment also improved testosterone levels and spermatogenesis, suggesting dual therapeutic potential for cancer and hypogonadism.
Area of Science:
- Oncology
- Endocrinology
- Molecular Biology
Background:
- HASPIN (Haploid germ cell-specific nuclear protein kinase) is a nuclear Ser/Thr kinase expressed in haploid germ cells.
- HASPIN kinase inhibitors have demonstrated antitumor activity.
- Colorectal cancer (CRC) is a prevalent malignancy with significant global incidence.
Purpose of the Study:
- To investigate the efficacy of the HASPIN inhibitor CHR-6494 in suppressing cancer progression in Apc mice, a model for familial colon tumor disease.
- To evaluate the impact of CHR-6494 on intestinal polyp development, body weight, testosterone levels, and spermatogenesis in Apc mice.
Main Methods:
- Apc mice were administered CHR-6494 via intraperitoneal injection for 50 days.
- Intestinal polyps were quantified post-treatment.
- Blood testosterone levels and spermatogenesis were assessed to evaluate endocrine and reproductive effects.
Main Results:
- Intraperitoneal CHR-6494 administration significantly inhibited intestinal polyp development in Apc mice.
- Treatment with CHR-6494 led to recovery of body weight in the Apc mice.
- CHR-6494 treatment significantly improved blood testosterone levels and spermatogenesis, counteracting age-related decline observed in Apc mice.
Conclusions:
- HASPIN inhibitors, exemplified by CHR-6494, show potential as anti-cancer agents for colorectal cancer.
- CHR-6494 may also be beneficial for treating hypogonadism in colorectal cancer patients.
- These findings highlight the dual therapeutic utility of targeting HASPIN in cancer and associated endocrine dysfunction.
