2-(allylthio)pyrazine suppresses the growth and proliferation of human promyelocytic leukemia (HL-60) cells via induction of apoptosis.
Apoptosis or programmed cell death is a highly organized physiologic process of not only maintaining homeostasis but also selectively eliminating damaged or abnormal cells. Apoptotic destruction of predisposed cells may reduce the proportion of cells available for malignant progression. Thus, pharmacologic manipulation of apoptotic pathway is regarded as a novel strategy in cancer chemoprevention as well as therapy. 2-(Allylthio)pyrazine (2-AP), a pyrazine derivative of allylsulfide synthesized for use as a chemoprotective agent, has been shown to protect against experimental carcinogenesis and mutagenesis. The present study examined the capability of 2-AP to induce apoptosis in cultured human promyelocytic leukemia (HL-60) cells. Treatment of HL-60 cells with 2-AP led to suppression of viability and proliferation in a concentration-dependent manner. Microscopic examination of the treated cells revealed typical morphological features of apoptosis, such as nuclear fragmentation and chromatin condensation. Furthermore, cells treated with 2-AP exhibited internucleosomal DNA fragmentation. Flow cytometric analysis of HL-60 cells exposed to 2-AP showed appearance of a distinct peak representing the subdiploid cell population. 2-AP treatment decreased the ratio of anti-apoptotic Bcl-2 to the death stimulating protein Bax, which may account for the molecular basis of apoptosis-inducing activity of this chemopreventive organosulfur derivative.
Lee
E
E
College of Pharmacy, Seoul National University, South Korea.
Kong
G
G
Lee
S J
SJ
Kim
N D
ND
Surh
Y J
YJ
D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002467:Cell Nucleus / Q000648:ultrastructure; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005434:Flow Cytometry; D018922:HL-60 Cells; D006801:Humans; D015151:Immunoblotting; D015473:Leukemia, Promyelocytic, Acute / Q000473:pathology*; D008854:Microscopy, Electron; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011719:Pyrazines / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein
C104935:2-(allylthio)pyrazine; C494826:BAX protein, human; D004791:Enzyme Inhibitors; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011719:Pyrazines; D051028:bcl-2-Associated X Protein