Piperlongumine Induces Apoptosis in Colorectal Cancer HCT 116 Cells Independent of Bax, p21 and p53 Status

• Published in: Anticancer research Vol. 38; no. 11; pp. 6231 - 6236
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Greece International Institute of Anticancer Research 01-11-2018
• Subjects: Acridine orange; Anticancer properties; Apoptosis; Bax protein; bcl-2-Associated X Protein - genetics; Cancer; Cell death; Cell Proliferation - drug effects; Cell Survival - drug effects; Circular dichroism; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - genetics; Cyclin-dependent kinase inhibitor p21; Cyclin-Dependent Kinase Inhibitor p21 - genetics; Deoxyribonucleic acid; Dichroism; Dioxolanes - pharmacology; DNA; Drug Screening Assays, Antitumor; Ethidium bromide; Flow cytometry; Gene Expression Regulation, Neoplastic - drug effects; HCT116 Cells; Humans; Mortality; p53 Protein; Plasmids; Proteins; Tumor Suppressor Protein p53 - genetics; Piperaceae; apoptosis; piperlongumine; Piper tuberculatum; colorectal cancer
• ISSN: 0250-7005; 1791-7530
• DOI: 10.21873/anticanres.12978

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.