Department of Pathobiology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand.
Pathobiology Information and Learning Center, Department of Pathobiology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand.
Int J Med Sci. 2023 Jul 24;20(9):1123-1134. doi: 10.7150/ijms.86573. eCollection 2023.
As colorectal cancer (CRC) usually presents at an advanced stage, it responds poorly to traditional surgery and chemoradiotherapy. Reactive oxygen species (ROSs) are a critical factor in cancer progression. Quercetin, a bioflavonoid derived from onion peel extract, provides great anti-oxidant and anti-cancer potential. Therefore, quercetin in combination with N-Acetylcysteine (NAC), a well-known anti-oxidant and adjuvant agent in cancer-chemotherapeutic drugs, was considered as a way of increasing treatment efficacy. Thus, this study aimed to evaluate the improvement effect of quercetin in combination with NAC in human CRC (HT-29 and HCT-116) cell progression, migration and invasion. Firstly, the effects of quercetin, NAC, and the combination of quercetin and NAC on cellular oxidants and glutathione levels were evaluated. Cell viability, anti-migrative activity and invasive activity were determined by MTT, wound healing, and Matrigel invasion tests, respectively. Then, the proteins involved in cell migration, invasion, and cellular oxidants were investigated. Moreover, the gene expression and overall survival were further validated by the GEPIA2 database. The results reveal that the combination was most effective in decreasing cellular oxidants and increasing glutathione levels, while there was a significant decrease in cancer cell migration and invasion involved in the suppression of iNOS, ICAM-1, and MMP-2 proteins. Furthermore, bioinformatic analysis verified that iNOS, ICAM-1, and MMP-2 were highly expressed in CRC tissue and also associated with a poor prognosis. This study demonstrated that Quercetin has higher efficacy when used in combination with NAC, representing a potential combination agent for anti-cancer drug development.
由于结直肠癌（CRC）通常处于晚期阶段，因此对传统手术和放化疗反应不佳。活性氧（ROS）是癌症进展的关键因素。槲皮素是一种从洋葱皮提取物中提取的生物类黄酮，具有强大的抗氧化和抗癌潜力。因此，将槲皮素与 N-乙酰半胱氨酸（NAC）结合使用，NAC 是癌症化疗药物中一种著名的抗氧化剂和辅助剂，被认为是提高治疗效果的一种方法。因此，本研究旨在评估槲皮素与 NAC 联合使用对人 CRC（HT-29 和 HCT-116）细胞进展、迁移和侵袭的改善作用。首先，评估了槲皮素、NAC 和槲皮素与 NAC 联合使用对细胞氧化剂和谷胱甘肽水平的影响。通过 MTT、划痕愈合和 Matrigel 侵袭试验分别测定细胞活力、抗迁移活性和侵袭活性。然后，研究了参与细胞迁移、侵袭和细胞氧化剂的蛋白质。此外，还通过 GEPIA2 数据库进一步验证了基因表达和总生存率。结果表明，联合用药在降低细胞氧化剂和增加谷胱甘肽水平方面最为有效，同时涉及 iNOS、ICAM-1 和 MMP-2 蛋白抑制的癌细胞迁移和侵袭也显著减少。此外，生物信息学分析验证了 iNOS、ICAM-1 和 MMP-2 在 CRC 组织中高表达，并且与预后不良相关。本研究表明，槲皮素与 NAC 联合使用具有更高的疗效，代表了开发抗癌药物的潜在联合药物。
