Piperlongumine Induces Apoptosis in Colorectal Cancer HCT 116 Cells Independent of Bax, p21 and p53 Status
Piperlongumine Induces Apoptosis in Colorectal Cancer HCT 116 Cells Independent of Bax, p21 and p53 Status
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DOI：
10.21873/anticanres.12978
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发表时间：
2018-11-01
影响因子：
2
通讯作者：
Roesch-Ely, Mariana
中科院分区：
文献类型：
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作者：
Machado, Fernanda Da Silva;Munari, Fernanda Mosena;Roesch-Ely, Mariana
背景/目的：结直肠癌是一种常见的癌症类型，在大多数情况下，由于细胞凋亡和细胞周期蛋白的功能丧失，报告了对治疗的抗性。鸡冠花碱（PPLGM）是从胡椒属植物中分离得到的一种天然生物碱，具有良好的抗癌活性。本研究调查了PPLGM是否能够诱导表达野生型或Bax、p21或p53缺陷的结肠直肠癌HCT 116细胞中的细胞死亡。材料与方法：从山胡椒根中提取PPLGM。通过3-（4，5-二甲基噻唑-2-基）-2，5-二苯基四唑溴化物（MTT）还原和克隆形成测定来测定细胞活力。通过吖啶橙子/溴化乙锭染色和流式细胞术评估细胞死亡。质粒切割活性和圆二色DNA相互作用进行了分析。结果如下：PPLGM诱导选择性细胞死亡的所有细胞系（IC 50范围从10.7至13.9 μ M）的晚期凋亡细胞的数量和细胞周期分布的不同配置文件的增加。质粒DNA分析表明，PPLGM不直接与DNA相互作用。结论：本文表明PPLGM可能是结直肠癌治疗的一个有希望的候选药物。
Background/Aim: Colorectal cancer is a common type of cancer with reported resistance to treatment, in most cases due to loss of function of apoptotic and cell-cycle proteins. Piperlongumine (PPLGM) is a natural alkaloid isolated from Piper species, with promising anti-cancer properties. This study investigated whether PPLGM is able to induce cell death in colorectal carcinoma HCT 116 cells expressing wild-type or deficient in Bax, p21 or p53. Materials and Methods: PPLGM was extracted from roots of Piper tuberculatum. Cell viability was determined by reduction of 3-(4,5-dimethilthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and clonogenic assay. Cell death was evaluated by acridine orange/ethidium bromide staining and flow cytometry. Plasmid cleavage activity and circular dichroism DNA interaction were also analyzed. Results: PPLGM induced selective cell death in all cell lines (IC50 range from 10.7 to 13.9 mu M) with an increase in the number of late apoptotic cells and different profiles in cell-cycle distribution. Plasmid DNA analysis showed that PPLGM does not interact directly with DNA. Conclusion: This paper suggests that PPLGM may be a promising candidate in colorectal cancer therapy.