马粟酸诱导人宫颈癌 HeLa 细胞 DNA 损伤并损害 DNA 修复。
Maslinic Acid Induces DNA Damage and Impairs DNA Repair in Human Cervical Cancer HeLa Cells.
机构信息
College of Chinese Medicine, School of Post-Baccalaureate Chinese Medicine, China Medical University, Taichung, Taiwan, R.O.C.
Department of Surgery, China Medical University Hospital, Taichung, Taiwan, R.O.C.
出版信息
Anticancer Res. 2020 Dec;40(12):6869-6877. doi: 10.21873/anticanres.14709.
BACKGROUND/AIM: Maslinic acid, a natural plant-derived triterpenoid compound, exhibits pharmacological activities, including anti-cancer. In the present study, we investigated the cytotoxic effects of maslinic acid on human cervical cancer HeLa cells in vitro and further investigated the molecular mechanism of maslinic acid-induced DNA damage and repair.
MATERIALS AND METHODS
Cell viability was measured by flow cytometry. DNA condensation (apoptotic cell death), DNA damage, and DNA fragmentation (DNA ladder) were assayed by DAPI staining, comet assay, and agarose gel electrophoresis, respectively. The expression of DNA damage and repair proteins was assayed by western blotting.
RESULTS
Maslinic acid decreased total cell viability and induced DNA condensation, damage, and fragmentation in HeLa cells. Furthermore, maslinic acid elevated the levels of p-ATM, p-ATR, p53, p-p53, p-H2A.X, BRCA1 and PARP at 30-40 μM. However, it decreased the levels of DNA-PK and MGMT.
CONCLUSION
Maslinic acid reduced the number of viable HeLa cells by inducing DNA damage and altering the expression of proteins involved in DNA damage and repair.
背景/目的：马粟酸是一种天然植物来源的三萜类化合物，具有多种药理学活性，包括抗癌作用。本研究旨在探讨马粟酸对体外培养的人宫颈癌 HeLa 细胞的细胞毒性作用，并进一步探讨马粟酸诱导的 DNA 损伤与修复的分子机制。
材料与方法
采用流式细胞术检测细胞活力。通过 DAPI 染色、彗星试验和琼脂糖凝胶电泳分别检测 DNA 凝聚（凋亡性细胞死亡）、DNA 损伤和 DNA 片段化（DNA 梯）。采用 Western blot 检测 DNA 损伤和修复蛋白的表达。
结果
马粟酸降低了 HeLa 细胞的总细胞活力，并诱导了 DNA 凝聚、损伤和片段化。此外，马粟酸在 30-40 μM 时升高了 p-ATM、p-ATR、p53、p-p53、p-H2AX、BRCA1 和 PARP 的水平，但降低了 DNA-PK 和 MGMT 的水平。
结论
马粟酸通过诱导 DNA 损伤和改变参与 DNA 损伤和修复的蛋白表达，减少了 HeLa 细胞的存活数量。
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