Department of Food Science and Nutrition; Zhejiang Key Laboratory for Agro-food Processing; Fuli Institute of Food Science; National Engineering Laboratory of Intelligent Food Technology and Equipment, Zhejiang University, Hangzhou 310058, People's Republic of China.
State Key Laboratory of Silicon Materials, School of Materials Science and Engineering, Zhejiang University, Hangzhou 310027, People's Republic of China.
Food Funct. 2021 Sep 20;12(18):8351-8365. doi: 10.1039/d1fo00581b.
Lung cancer has been threatening human health worldwide for a long time. However, the clinic therapies remain unsatisfactory. In this study, the anti-adenocarcinoma lung cancer A549 cell line abilities of tuber flavonoids (THTF) were evaluated , and isobaric tags for relative and absolute quantification (iTRAQ)-based proteomic analysis was conducted to detect the protein alterations in THTF-treated solid tumors. The differentially expressed proteins were related to the cytoskeleton and mostly accumulated in the calcium signaling pathway. The study illustrated that 80 μg mL THTF significantly suppressed cellular viability to approximately 75% of the control. Further results suggested that kaempferol-3--rutinoside (K3R), the major component of THTF, effectively triggered cytoskeleton collapse, mitochondrial dysfunction and consequent calcium overload to achieve apoptosis, which remained consistent with proteomic results. This study uncovers a new mechanism for THTF anti-tumor ability, and suggests THTF and K3R as promising anti-cancer agents, providing new ideas and possible strategies for future anti-lung cancer prevention and therapy.
肺癌长期以来一直威胁着全球人类的健康。然而,临床治疗仍然不尽如人意。在本研究中,评估了 山柰酚黄酮(THTF)对人肺腺癌细胞系 A549 的抗癌作用,并进行了基于等重标记相对和绝对定量(iTRAQ)的蛋白质组学分析,以检测 THTF 处理的实体瘤中的蛋白质变化。差异表达的蛋白质与细胞骨架有关,并且主要在钙信号通路中积累。研究表明,80μg mL 的 THTF 可显著抑制细胞活力,使其约为对照的 75%。进一步的结果表明,THTF 的主要成分山柰酚-3-O-芸香糖苷(K3R)可有效触发细胞骨架崩溃、线粒体功能障碍和随后的钙超载,从而实现细胞凋亡,这与蛋白质组学结果一致。本研究揭示了 THTF 抗肿瘤能力的新机制,并表明 THTF 和 K3R 可能成为有前途的抗癌药物,为未来的肺癌预防和治疗提供了新的思路和可能的策略。