雷尼替酶素 T 衍生物 DH_22 诱导肺癌细胞中 p53 依赖性凋亡。
Renieramycin T Derivative DH_22 Induces p53-dependent Apoptosis in Lung Cancer Cells.
机构信息
Center of Excellence in Cancer Cell and Molecular Biology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.
Graduate Program of Pharmaceutical Sciences and Technology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.
出版信息
In Vivo. 2023 Sep-Oct;37(5):1960-1966. doi: 10.21873/invivo.13292.
BACKGROUND/AIM: Targeting apoptotic pathways has been identified as a promising strategy for the treatment of lung cancer. We synthesized a new derivative of renieramycin T (RT), named DH_22, and examined its anticancer activities in human lung cancer cells.
MATERIALS AND METHODS
The RT derivative DH_22 was chemically modified from RT. The apoptosis-inducing effect was evaluated in A549 cells by annexin V-FITC/PI staining and nuclear staining assay (Hoechst/PI). In addition, the molecular pathway was analyzed by western blot analysis.
RESULTS
In the cell viability and nuclear staining tests, DH_22 was discovered to be cytotoxic with an IC of 13.27 μM; it induced apoptosis of lung cancer cells. Regarding the mechanism, DH_22 contributed to the activation of p53-dependent apoptosis and decreased the cellular level of c-Myc. The p53-dependent mechanism was indicated by an increase in p53, an induction of the pro-apoptotic Bax protein, and a decrease in the anti-apoptotic B-cell lymphoma 2 (Bcl-2) protein.
CONCLUSION
DH_22 has great potential for further development as a new anticancer drug.
背景/目的：靶向细胞凋亡途径已被确定为治疗肺癌的一种有前途的策略。我们合成了一种雷尼霉素 T（RT）的新衍生物，命名为 DH_22，并研究了其在人肺癌细胞中的抗癌活性。
材料和方法
RT 衍生物 DH_22 是从 RT 化学修饰而来的。通过 Annexin V-FITC/PI 染色和核染色（Hoechst/PI）实验评估 A549 细胞中的凋亡诱导作用。此外，通过 Western blot 分析研究了分子途径。
结果
在细胞活力和核染色试验中，DH_22 的 IC 为 13.27 μM，具有细胞毒性，诱导肺癌细胞凋亡。关于其机制，DH_22 有助于激活 p53 依赖性凋亡并降低细胞内 c-Myc 水平。p53 依赖性机制表现为 p53 增加、促凋亡 Bax 蛋白诱导和抗凋亡 B 细胞淋巴瘤 2（Bcl-2）蛋白减少。
结论
DH_22 作为一种新型抗癌药物具有很大的发展潜力。
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