title: Induction of apoptosis by 7-piperazinethylchrysin in HCT-116 human colon             cancer cells.
abstract: The antitumor activity of 7-piperazinethylchrysin (7-PEC) was investigated in HCT-116 human colon cancer cells. MTT assay revealed that the IC50 of 7-PEC in HCT-116 cells was 1.5 µM after 72 h of treatment, much lower than that of chrysin (>100 µM). The data showed that 7-PEC was able to inhibit the growth of HCT-116 cells in a concentration- and time-dependent manner. Topical morphological changes of apoptotic body formation after 7-PEC treatment were observed by Hoechst 33258 staining. 7-PEC reduced mitochondrial membrane potential (∆Ψm) of cells in a concentration-dependent manner and increased the production of intracellular reactive oxygen species (ROS). After treatment with 7-PEC, a significant increase of Bax protein expression and decrease of Bcl-2 protein expression were observed at the same time. These events paralleled with activation of p53, caspase-3 and -9 and the release of cytochrome c (cyt‑c), as well as poly(ADP-ribose) polymerase-1 (PARP1) cleavage and downregulation of p-Akt. However, the apoptosis induced by 7-PEC was blocked by Ac-DEVD-CHO, a caspase-3 inhibitor. These results demonstrate that 7-PEC-induced mitochondrial dysfunction in HCT-116 human colon cancer cells triggers events responsible for caspase-dependent apoptosis pathways, and the elevated ratio of Bax/Bcl-2 is likely involved in this effect.
authors.affiliation: School of Pharmaceutical Engineering and Life Science, Changzhou University, Changzhou, Jiangsu 213164, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Ren
authors.forename: Hong
authors.initials: H
authors.lastname: Cheng
authors.forename: Wen Qun
authors.initials: WQ
authors.lastname: Xin
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.forename: Kun
authors.initials: K
authors.lastname: Hu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000096:biosynthesis; D053453:Caspase 9 / Q000096:biosynthesis; D061945:Caspase Inhibitors / Q000494:pharmacology; D002470:Cell Survival; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D045304:Cytochromes c / Q000378:metabolism; D015536:Down-Regulation; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D045325:HCT116 Cells; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology; D010879:Piperazines / Q000737:chemistry / Q000494:pharmacology*; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000096:biosynthesis; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis
chemical_list: C578838:7-piperazinethylchrysin; D000970:Antineoplastic Agents; D061945:Caspase Inhibitors; D005419:Flavonoids; D009842:Oligopeptides; D010879:Piperazines; D017382:Reactive Oxygen Species; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C099158:acetyl-aspartyl-glutamyl-valyl-aspartal; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; C043561:chrysin; D045304:Cytochromes c; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3; D053453:Caspase 9