Wang Jui-Ho, Chen Yun-Wen, Hsieh Shuchen, Kung Mei-Lang
Division of Colon and Rectal Surgery, Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
Departments of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Environ Toxicol. 2025 Aug;40(8):1059-1071. doi: 10.1002/tox.24470. Epub 2025 Feb 25.
Colorectal cancer (CRC) has become one of the most arduous challenges in contemporary cancer treatment. In nanomedicine, biomedical methodologies and nanomaterials are combined to develop novel and effective treatments for illnesses, infections, and cancer. The characteristics of nanotechnology are promising for addressing the urgent problems of modern cancer therapeutics, such as tumor recurrence, multidrug resistance, and the limited accessibility of drugs to tumor tissue. Plant-derived natural chemicals, termed phytochemicals, have bioactive characteristics, including anticarcinogenesis, promoted cell apoptosis, antioxidation, antiproliferation, and anti-inflammatory effects. Zingerone is a phenolic compound; it is one of the nonvolatile pungent constituents of ginger and has various pharmacological activities. Here, we fabricated phytochemical-derived zingerone nanoparticles (NPs) and explored their anti-cell viability and anti-tumorigenicity effects on human CRC LoVo and HCT116 cell lines. Moreover, zingerone NPs significantly inhibited cell viability and in vitro tumorigenicity. Next, flow cytometry analysis revealed that zingerone NPs markedly suppressed cell cycle progression in the G2/M phase compared to the G1/S phase and significantly promoted cell apoptosis in a dose-dependent manner in these CRC cell lines. Western blot analysis also suggested that zingerone NPs mediate cell apoptosis by upregulating caspase 3/PARP signaling. Additionally, zingerone NPs significantly restricted CDC25C-mediated CDK1/Cyclin B1 signaling activation in the G2/M phase and Cyclin D/CDK2/Cyclin A signaling downregulation in the G1/S phase. Zingerone NP-mediated p21 upregulation also decreased CDK activity and interfered with cell cycle progression. Indeed, TCGA data analysis also suggested that CDC25C and CDK1 upregulation were correlated with advanced tumor stage in colorectal cancer patients. Taken together, these results indicated that zingerone NPs significantly disrupt cell cycle progression and induce apoptosis in human CRC cells. Our findings indicate that phytochemical-derived zingerone NPs may serve as a potential chemopreventive adjuvant agent and therapeutic strategy for human colorectal cancer.
结直肠癌（CRC）已成为当代癌症治疗中最艰巨的挑战之一。在纳米医学中，生物医学方法与纳米材料相结合，以开发针对疾病、感染和癌症的新型有效治疗方法。纳米技术的特性有望解决现代癌症治疗中的紧迫问题，如肿瘤复发、多药耐药性以及药物对肿瘤组织的可及性有限等问题。植物来源的天然化学物质，即植物化学物，具有生物活性特性，包括抗癌发生、促进细胞凋亡、抗氧化、抗增殖和抗炎作用。姜辣素是一种酚类化合物；它是生姜的非挥发性辛辣成分之一，具有多种药理活性。在此，我们制备了植物化学物衍生的姜辣素纳米颗粒（NPs），并探讨了它们对人CRC LoVo和HCT116细胞系的抗细胞活力和抗肿瘤发生作用。此外，姜辣素纳米颗粒显著抑制细胞活力和体外肿瘤发生能力。接下来，流式细胞术分析显示，与G1/S期相比，姜辣素纳米颗粒在G2/M期显著抑制细胞周期进程，并在这些CRC细胞系中以剂量依赖性方式显著促进细胞凋亡。蛋白质免疫印迹分析还表明，姜辣素纳米颗粒通过上调半胱天冬酶3/聚（ADP-核糖）聚合酶（PARP）信号传导介导细胞凋亡。此外，姜辣素纳米颗粒在G2/M期显著限制细胞分裂周期蛋白25C（CDC25C）介导的细胞周期蛋白依赖性激酶1（CDK1）/细胞周期蛋白B1信号激活，在G1/S期显著下调细胞周期蛋白D/细胞周期蛋白依赖性激酶2（CDK2）/细胞周期蛋白A信号。姜辣素纳米颗粒介导的p21上调也降低了CDK活性并干扰细胞周期进程。事实上，癌症基因组图谱（TCGA）数据分析还表明，CDC25C和CDK1上调与结直肠癌患者的晚期肿瘤分期相关。综上所述，这些结果表明姜辣素纳米颗粒显著破坏人CRC细胞的细胞周期进程并诱导细胞凋亡。我们的研究结果表明，植物化学物衍生的姜辣素纳米颗粒可能作为人类结直肠癌的潜在化学预防辅助剂和治疗策略。
