Novel compound NHWD-870 suppresses melanoma proliferation by inducing cell cycle arrest and apoptosis
Introduction: Malignant melanoma is the most aggressive form of skin cancer worldwide. Although various novel therapies, including targeted therapies, immunotherapies, and epigenetic therapies, have been developed in recent decades to provide new treatment options, most patients with melanoma either respond poorly or develop resistance quickly. Thus, new therapeutic options are urgently needed. Bromodomain and extra-terminal domain (BET) inhibition has emerged as a potential therapeutic strategy in cancer treatment.
Objectives: We aimed to study the effects of NHWD-870, a novel BET inhibitor analogue of BMS-986158, on melanoma proliferation.
Methods: We examined the effects of BMS-986158 and NHWD-870 on tumor proliferation in vitro and in vivo using the Cell Counting Kit-8 assay, Ki67-positive cell analysis, colony formation assay, and a xenograft mouse model. Flow cytometry and Western blotting were performed to investigate the effects of NHWD-870 on melanoma cell cycle and apoptosis.
Results: We found that NHWD-870 exhibited improved ability to suppress melanoma cell proliferation both in vitro and in vivo compared to BMS-986158. Mechanistically, NHWD-870 treatment induced G2/M cell cycle arrest and apoptosis, accompanied by decreased cyclin B1 levels.
Conclusion: Our results suggest that NHWD-870 exhibits effective antineoplastic potency. It effectively inhibits melanoma progression, demonstrating greater efficacy than BMS-986158. These findings support further development of NHWD-870 as a potential new therapeutic candidate for melanoma treatment.
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