Department of Chemistry, Xavier University of Louisiana.
Cell and Molecular Biology and Bioinformatic Core, College of Pharmacy, Xavier University of Louisiana.
Anticancer Drugs. 2024 Jan 1;35(1):12-21. doi: 10.1097/CAD.0000000000001536. Epub 2023 Aug 15.
Ceramides are known to show anti-cancer activity. A novel ceramide analog, (S,E)-3-hydroxy-2-(2-hydroxybenzylidene)amino-N-tetradecylpropanamide (analog 315) was developed as part of a larger study focused on finding more effective breast cancer treatments.
To assess whether analog 315 shows any or a combination of the following effects in breast cancer cells in vitro: inhibiting proliferation, inducing apoptosis, and altering protein expression. Also, to determine whether it inhibits chemo-resistant breast cancer tumor growth in vivo mouse model.
In vitro cell proliferation and apoptosis after treatment with analog 315 were assessed in three breast cancer cell lines (MCF-7, MCF-7TN-R, and MDA-MB-231) and reported. Protein expression was assessed by microarray assay. For the in vivo studies, chemo-resistant breast cancer cells were used for tumor development in two groups of mice (treated and control). Analog 315 (25 mg/kg/day) or control (dimethyl sulfoxide) was administered intraperitoneally for 7 days. Effects of analog 315 on inhibiting the growth of chemo-resistant breast cancer tumors after treatment are reported.
Analog 315 reduced MCF-7TN-R chemo-resistant tumor burden (volume and weight) in mice. Liver metastasis was observed in control mice, but not in the treated animals. Ki-67, a proliferation marker for breast cancer cells, increased significantly ( P < 0.05) in control tumor tissue. In vitro studies showed that analog 315 inhibited cell proliferation, altered protein expression and induced apoptosis in all three breast cancer cell lines studied, of which the effects on MCF-7TN-R cells were the most significant.
Analog 315 reduced tumor growth in chemo-resistant breast cancer, inhibited cell proliferation, altered protein expression, and induced apoptosis in all three cell lines studied.
神经酰胺具有抗癌活性。作为一项旨在寻找更有效的乳腺癌治疗方法的大型研究的一部分，开发了一种新型神经酰胺类似物（S，E）-3-羟基-2-（2-羟基苯亚甲基）氨基-N-十四烷基丙酰胺（类似物 315）。
评估类似物 315 是否在体外乳腺癌细胞中表现出以下任何一种或多种作用：抑制增殖，诱导细胞凋亡和改变蛋白表达。还确定它是否抑制体内耐化疗的乳腺癌肿瘤生长的小鼠模型。
在三种乳腺癌细胞系（MCF-7、MCF-7TN-R 和 MDA-MB-231）中评估类似物 315 处理后的细胞增殖和细胞凋亡，并进行报道。通过微阵列分析评估蛋白表达。对于体内研究，使用耐化疗的乳腺癌细胞在两组小鼠（治疗组和对照组）中进行肿瘤发展。以腹腔内给药的方式给予类似物 315（25mg/kg/天）或对照（二甲亚砜）7 天。报道类似物 315 对治疗后耐化疗的乳腺癌肿瘤生长的抑制作用。
类似物 315 降低了 MCF-7TN-R 耐化疗肿瘤的小鼠负担（体积和重量）。在对照组小鼠中观察到肝转移，但在治疗组动物中未观察到。乳腺癌细胞增殖标志物 Ki-67 在对照组肿瘤组织中显著增加（P ＜0.05）。体外研究表明，类似物 315 抑制细胞增殖，改变三种研究的乳腺癌细胞系中的蛋白表达，并诱导细胞凋亡，其中对 MCF-7TN-R 细胞的作用最为显著。
类似物 315 降低了耐化疗的乳腺癌肿瘤生长，抑制了细胞增殖，改变了三种研究的细胞系中的蛋白表达，并诱导了细胞凋亡。
