Apoptotic-inducing activity of novel polycyclic aromatic compounds in human leukemic cells.
Persistent but relatively limited research has been devoted to the use of compounds related to polycyclic aromatic hydrocarbons (PAH) as anticancer agents. In previous reports, we have described the cytotoxicity of a number of new and novel PAH against human cancer cell lines. However, the involved molecular mechanisms of inducing cell death were not elucidated. In the current study, we describe the apoptotic pathway as apparently playing a crucial role in induced cell death in human leukemia Jurkat T cells by several diamide and diamine PAH that contain chrysene as their core aromatic ring system. Structure-activity relationships were analyzed. Importantly, no effect was demonstrated in a normal, non-transformed line of human natural killer cells. These results provide additional evidence for the potential chemotherapeutic use of PAH.
Landis-Piwowar
Kristin R
KR
The Prevention Program, Barbara Ann Karmanos Cancer Institute, and Department of Pathology, School of Medicine, Wayne State University, Detroit, MI 48201, USA.
Chen
Di
D
Cui
Qiuzhi Cindy
QC
Minic
Vesna
V
Becker
Frederick F
FF
Banik
Bimal K
BK
Dou
Q Ping
QP
D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002911:Chrysenes / Q000737:chemistry / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D020287:In Situ Nick-End Labeling; D019169:Jurkat Cells; D007694:Killer Cells, Natural / Q000166:cytology / Q000187:drug effects; D007938:Leukemia / Q000378:metabolism / Q000473:pathology; D015394:Molecular Structure; D010879:Piperazines / Q000737:chemistry / Q000494:pharmacology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011084:Polycyclic Aromatic Hydrocarbons / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D002911:Chrysenes; D010879:Piperazines; D011084:Polycyclic Aromatic Hydrocarbons; C514250:Tx-1 compound; C514251:Tx-23 compound; D011065:Poly(ADP-ribose) Polymerases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases