Prasad Yenisetti Rajendra, Anakha J, Jawalekar Snehal Sainath, Pande Abhay H
Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, Mohali, S.A.S. Nagar, 160062, Punjab, India.
Invest New Drugs. 2024 Oct;42(5):531-537. doi: 10.1007/s10637-024-01466-8. Epub 2024 Aug 20.
The rapid increase in cancer cases worldwide necessitates the development of novel therapeutic approaches. Therapies targeting cancer's altered metabolism, especially those that deplete critical amino acids, have emerged as promising ones, some of which are already being used in clinical practice and many others are under development. This study reports the anti-cancer activity of two novel fused human arginase I (FHA) variants, FHA-3 and FHA-12, assessed using the NCI-60 human tumor cell line panel. Both variants have demonstrated a range of potencies in a single-dose assay (10 µM), but FHA-3 was found to be more potent with significant growth inhibition in most tested cell lines. To calculate 50% growth inhibition (GI), FHA-3 was further evaluated in a five-dose assay, where notable anti-cancer activity was observed across the nine cancer types of the NCI-60 panel. Our results demonstrated the broad-spectrum anti-cancer activity of novel FHA variants, with FHA-3 being the most potent. Further studies elucidating its efficacy in animal models will help explore its therapeutic potential.
全球癌症病例的迅速增加使得开发新的治疗方法成为必要。针对癌症代谢改变的疗法，尤其是那些消耗关键氨基酸的疗法，已成为有前景的疗法，其中一些已在临床实践中使用，还有许多正在研发中。本研究报告了两种新型融合人精氨酸酶I（FHA）变体FHA - 3和FHA - 12的抗癌活性，使用NCI - 60人肿瘤细胞系面板进行评估。两种变体在单剂量试验（10 μM）中均表现出一系列效力，但发现FHA - 3效力更强，在大多数测试细胞系中具有显著的生长抑制作用。为了计算50%生长抑制率（GI），在五剂量试验中对FHA - 3进行了进一步评估，在NCI - 60面板的九种癌症类型中均观察到显著的抗癌活性。我们的结果证明了新型FHA变体的广谱抗癌活性，其中FHA - 3效力最强。进一步阐明其在动物模型中疗效的研究将有助于探索其治疗潜力。
