DA Silva Machado Fernanda, Munari Fernanda Mosena, Scariot Fernando Joel, Echeverrigaray Sergio, Aguzzoli Cesar, Pich Claus Tröger, Kato Massuo Jorge, Yamaguchi Lydia, Moura Sidnei, Henriques João Antonio Pêgas, Roesch-Ely Mariana
Laboratory of Genomics, Proteomics and DNA Repair, Biotechnology Institute, University of Caxias do Sul, Caxias do Sul, Brazil.
Laboratory of Genomics, Proteomics and DNA Repair, Biotechnology Institute, University of Caxias do Sul, Caxias do Sul, Brazil
Anticancer Res. 2018 Nov;38(11):6231-6236. doi: 10.21873/anticanres.12978.
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.
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.
PPLGM induced selective cell death in all cell lines (IC range from 10.7 to 13.9 μM) 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.
This paper suggests that PPLGM may be a promising candidate in colorectal cancer therapy.
背景/目的:结直肠癌是一种常见的癌症类型,据报道对治疗具有抗性,在大多数情况下是由于凋亡蛋白和细胞周期蛋白功能丧失所致。胡椒碱(PPLGM)是从胡椒属植物中分离出的一种天然生物碱,具有良好的抗癌特性。本研究调查了PPLGM是否能够诱导表达野生型或缺乏Bax、p21或p53的结直肠癌HCT 116细胞发生细胞死亡。
从糙果胡椒根中提取PPLGM。通过3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐(MTT)还原法和克隆形成试验测定细胞活力。通过吖啶橙/溴化乙锭染色和流式细胞术评估细胞死亡情况。还分析了质粒切割活性和圆二色性DNA相互作用。
PPLGM在所有细胞系中均诱导选择性细胞死亡(IC范围为10.7至13.9 μM),晚期凋亡细胞数量增加且细胞周期分布呈现不同特征。质粒DNA分析表明PPLGM不直接与DNA相互作用。
本文表明PPLGM可能是结直肠癌治疗中一个有前景的候选药物。