Islam Atikul, Chang Yu-Chun, Tsao Nai-Wen, Wang Sheng-Yang, Chueh Pin Ju
Institute of Biomedical Sciences, National Chung Hsing University, Taichung 40227, Taiwan.
Special Crop and Metabolome Discipline Cluster, Academy Circle Economy, National Chung Hsing University, Taichung City 402202, Taiwan.
Antioxidants (Basel). 2024 Feb 26;13(3):284. doi: 10.3390/antiox13030284.
Colorectal cancer is the most common cancer that affects both sexes and has a poor prognosis due to aggressiveness and chemoresistance. Essential oils isolated from (CF-EOs) have been shown to demonstrate anti-termite, antifungal, anti-mosquito, and anti-microbial activities. However, the anticancer effects of CF-EOs are not yet fully understood. Therefore, the present study aimed to explore the molecular mechanism underlying CF-EOs-mediated anti-proliferative activity in colon cancer cells. Here, cell impedance measurements showed that CF-EOs inhibit proliferation in colon cancer cells with wild-type or mutant p53. Flow cytometry revealed that CF-EOs at 20, 50 µg/mL significantly induced ROS generation and autophagy in both HCT116 p53-wt and HCT116 p53-null cell lines, whereas pretreatment with the ROS scavenger N-acetyl cysteine (NAC) markedly attenuated these changes. CF-EOs also induced apoptosis at 50 µg/mL in both lines, as determined by flow cytometry. Protein analysis showed that CF-EOs markedly induced apoptosis markers, including Trail, cleaved caspase-3, cleaved caspase-9, and cleaved PARP, as well as autophagy markers, such as the levels of ULK1, Atg5, Atg6, Atg7, and the conversion of LC3-I to LC3-II. CF-EOs were further found to inhibit the activity and expression of the NAD-dependent deacetylase SIRT1 to increase the levels of acetylated p53 (Ac-p53) in p53-wt cells and acetylated c-Myc (Ac-c-Myc) in p53-null cells, ultimately inducing apoptosis in both lines. Interestingly, suppression of SIRT1 by CF-EOs enhanced the acetylation of ULK1, which in turn prompted ROS-dependent autophagy in colon cancer cells. The induction of apoptosis and autophagy by CF-EOs suggests that they may have potential as a promising new approach for treating cancer. Collectively, our results suggest that essential oils isolated from act as a promising anticancer agent against colon cancer cells by targeting SIRT1 to induce ROS-mediated autophagy and apoptosis.
结直肠癌是影响两性的最常见癌症，由于其侵袭性和化疗耐药性，预后较差。从[具体来源未给出]分离出的香精油（CF-EOs）已显示出具有抗白蚁、抗真菌、抗蚊虫和抗菌活性。然而，CF-EOs的抗癌作用尚未完全了解。因此，本研究旨在探讨CF-EOs介导的结肠癌细胞抗增殖活性的分子机制。在此，细胞阻抗测量表明CF-EOs抑制野生型或突变型p53结肠癌细胞的增殖。流式细胞术显示，20、50μg/mL的CF-EOs在HCT116 p53-wt和HCT116 p53-null细胞系中均显著诱导活性氧（ROS）生成和自噬，而用ROS清除剂N-乙酰半胱氨酸（NAC）预处理可显著减弱这些变化。流式细胞术测定结果表明，CF-EOs在50μg/mL时也诱导两细胞系发生凋亡。蛋白质分析表明，CF-EOs显著诱导凋亡标志物，包括肿瘤坏死因子相关凋亡诱导配体（Trail）、裂解的半胱天冬酶-3、裂解的半胱天冬酶-9和裂解的聚（ADP-核糖）聚合酶（PARP），以及自噬标志物，如UNC-51样激酶1（ULK1）、自噬相关蛋白5（Atg5）、自噬相关蛋白6（Atg6）、自噬相关蛋白7（Atg7）的水平以及微管相关蛋白1轻链3-I（LC3-I）向微管相关蛋白1轻链3-II（LC3-II）的转化。进一步发现CF-EOs抑制NAD依赖性脱乙酰酶沉默信息调节因子1（SIRT1）的活性和表达，以增加p53-wt细胞中乙酰化p53（Ac-p53）的水平和p53-null细胞中乙酰化c-Myc（Ac-c-Myc）的水平，最终诱导两细胞系凋亡。有趣的是，CF-EOs对SIRT1的抑制增强了ULK1的乙酰化，这反过来又促使结肠癌细胞中ROS依赖性自噬。CF-EOs诱导凋亡和自噬表明它们可能是一种有前途的癌症治疗新方法。总体而言，我们的结果表明，从[具体来源未给出]分离出的香精油通过靶向SIRT1诱导ROS介导的自噬和凋亡，作为一种有前途的抗结肠癌细胞的抗癌剂。
