Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway 47500, Selangor Darul Ehsan, Malaysia.
Natural Medicine and Product Research Laboratory, Institute of Bioscience, University Putra Malaysia, Serdang 43400, Selangor Darul Ehsan, Malaysia.
Int J Mol Sci. 2024 Mar 20;25(6):3503. doi: 10.3390/ijms25063503.
Diarylpentanoids are synthesized to overcome curcumin's poor bioavailability and low stability to show enhanced anti-cancer effects. Little is known about the anti-cancer effects of diarylpentanoid MS17 (1,5-bis(2-hydroxyphenyl)-1,4-pentadiene-3-one) in colon cancer cells. This study aimed to elucidate molecular mechanisms and pathways modulated by MS17 in colon cancer based on proteomic profiling of primary SW480 and metastatic SW620 colon cancer cells. Cytotoxicity and apoptotic effects of MS17 were investigated using MTT assay, morphological studies, and Simple Western analysis. Proteomic profiling using LC/MS analysis identified differentially expressed proteins (DEPs) in MS17-treated cells, with further analysis in protein classification, gene ontology enrichment, protein-protein interaction network and Reactome pathway analysis. MS17 had lower EC values (SW480: 4.10 µM; SW620: 2.50 µM) than curcumin (SW480: 17.50 µM; SW620: 13.10 µM) with a greater anti-proliferative effect. MS17 treatment of 1× EC induced apoptotic changes in the morphology of SW480 and SW620 cells upon 24 h treatment. A total of 24 and 92 DEPs (fold change ≥ 1.50) were identified in SW480 and SW620 cells, respectively, upon MS17 treatment of 2× EC for 24 h. Pathway analysis showed that MS17 may induce its anti-cancer effects in both cells via selected DEPs associated with the top enriched molecular pathways. RPL and RPS ribosomal proteins, heat shock proteins (HSPs) and ubiquitin-protein ligases (UBB and UBC) were significantly associated with cellular responses to stress in SW480 and SW620 cells. Our findings suggest that MS17 may facilitate the anti-proliferative and apoptotic activities in primary (SW480) and metastatic (SW620) human colon cancer cells via the cellular responses to stress pathway. Further investigation is essential to determine the alternative apoptotic mechanisms of MS17 that are independent of caspase-3 activity and Bcl-2 protein expression in these cells. MS17 could be a potential anti-cancer agent in primary and metastatic colon cancer cells.
二芳基戊烷类化合物被合成出来以克服姜黄素生物利用度差和稳定性低的问题，从而显示出增强的抗癌作用。目前对于二芳基戊烷类化合物 MS17（1,5-双（2-羟基苯基）-1,4-戊二烯-3-酮）在结肠癌细胞中的抗癌作用知之甚少。本研究旨在基于原发性 SW480 和转移性 SW620 结肠癌细胞的蛋白质组谱分析，阐明 MS17 调节的分子机制和途径。使用 MTT 测定法、形态学研究和 Simple Western 分析研究了 MS17 的细胞毒性和凋亡作用。使用 LC/MS 分析进行蛋白质组谱分析，鉴定了 MS17 处理细胞中差异表达的蛋白质 (DEP)，进一步进行蛋白质分类、基因本体富集、蛋白质-蛋白质相互作用网络和 Reactome 途径分析。MS17 的 EC 值（SW480：4.10 µM；SW620：2.50 µM）低于姜黄素（SW480：17.50 µM；SW620：13.10 µM），具有更强的抗增殖作用。在 24 小时处理后，MS17 以 1×EC 处理诱导 SW480 和 SW620 细胞形态发生凋亡变化。在用 2×EC 处理 24 小时后，分别在 SW480 和 SW620 细胞中鉴定出 24 和 92 个 DEP（倍数变化≥1.50）。途径分析表明，MS17 可能通过与顶级富集分子途径相关的选定 DEP 诱导两种细胞的抗癌作用。RPL 和 RPS 核糖体蛋白、热休克蛋白 (HSPs) 和泛素蛋白连接酶 (UBB 和 UBC) 与 SW480 和 SW620 细胞对压力的细胞反应显著相关。我们的研究结果表明，MS17 可能通过细胞对压力途径促进原发性（SW480）和转移性（SW620）人结肠癌细胞的增殖抑制和凋亡活性。进一步的研究对于确定 MS17 在这些细胞中独立于 caspase-3 活性和 Bcl-2 蛋白表达的替代凋亡机制是必要的。MS17 可能是原发性和转移性结肠癌细胞的潜在抗癌药物。
Zotero 插件
