Department of Pharmacology and Toxicology, Unversity of Otago, 18 Frederick Street, Dunedin, 9085, New Zealand.
Flint Animal Cancer Center, Colorado State University, Fort Collins, CO, USA.
Vet Res Commun. 2024 Feb;48(1):563-568. doi: 10.1007/s11259-023-10201-2. Epub 2023 Aug 19.
Canine histiocytic sarcoma is an aggressive cancer, with a high rate of metastasis. Thus, novel therapeutic approaches are needed. Synthetic analogues of curcumin have elicited potent anti-cancer activity in multiple in vitro and in vivo models of human cancer. Furthermore, the compound 3,5-bis(3,4,5-trimethoxybenzylidene)-1-methylpiperidine-4-one (RL71) has recently exhibited potent cell cycle arrest and apoptotic induction in a canine osteosarcoma cell line. To determine its potency in canine histiocytic sarcoma cells, cell viability of DH82 and Nike cells was measured using the sulforhodamine B assay. Flow cytometry was then used to analyse both cell cycle distribution and apoptosis. Of the five curcumin analogues examined, RL71, had the highest potency with EC values of 0.66 ± 0.057 µM and 0.79 ± 0.13 µM in the DH82 and Nike cell lines, respectively. Furthermore, RL71 at the 1x EC concentration increased G2/M cell cycle arrest 2-fold, and at the 2x EC concentration increased the number of apoptotic cells 4-fold. These findings are consistent with previous work using RL71 in both canine and human cancer cell lines. Future research should be directed on time-dependent changes, and mechanistic investigation in greater detail to elucidate RL71 mechanisms of action.
犬组织细胞肉瘤是一种侵袭性癌症，转移率很高。因此，需要新的治疗方法。姜黄素的合成类似物在多种人类癌症的体外和体内模型中表现出了很强的抗癌活性。此外，化合物 3,5-双（3,4,5-三甲氧基苯亚甲基）-1-甲基哌啶-4-酮（RL71）最近在犬骨肉瘤细胞系中表现出很强的细胞周期停滞和凋亡诱导作用。为了确定其在犬组织细胞肉瘤细胞中的效力，使用磺酰罗丹明 B 测定法测量 DH82 和 Nike 细胞的细胞活力。然后使用流式细胞术分析细胞周期分布和细胞凋亡。在研究的五种姜黄素类似物中，RL71 对 DH82 和 Nike 细胞系的 EC 值分别为 0.66 ± 0.057 µM 和 0.79 ± 0.13 µM，具有最高的效力。此外，RL71 在 1xEC 浓度下使 G2/M 细胞周期停滞增加了 2 倍，在 2xEC 浓度下使凋亡细胞数量增加了 4 倍。这些发现与 RL71 在犬和人类癌细胞系中的先前工作一致。未来的研究应该集中在时间依赖性变化上，并更详细地进行机制研究，以阐明 RL71 的作用机制。
