Endomorphins, endogenous opioid peptides, induce apoptosis in human leukemia HL-60 cells.
Opioids play a role in the apoptosis machinery. We studied the induction of apoptosis in endomorphin 1 (EM1) and endomorphin 2 (EM2), 2 newly isolated endogenous mu-opioid receptor agonists. These endomorphins were able to reduce the viability of cultured HL-60 cells. The antiproliferative properties of endomorphins appeared to be attributable to their induction of apoptotic cell death as determined by ultrastructural change, internucleosomal DNA fragmentation, and increased proportion of the subdiploid cell population. To elucidate molecular events in the apoptosis, protein expressions of Bcl-2, Bax, Fas, and FasL were measured by western blotting using specific antibodies in HL-60 cells. The level of Bcl-2 indicated down-regulation, but the Bax, Fas, and FasL expression showed up-regulation as compared with the untreated control cells. These data support the idea that endomorphins induce apoptosis in HL-60 cells through the activation of the Bcl-2-Bax and the Fas-FasL pathway. We suggest that endomorphins may play an important role in the regulation of tumor cell death.
Lin
Xin
X
Department of Biochemistry and Molecular Biology, School of Life Science, Lanzhou University, China.
Chen
Qiang
Q
Xue
Li-Ying
LY
Ma
Xiao-Jun
XJ
Wang
Rui
R
D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D053938:DNA Fragmentation / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D019254:Genes, bcl-2 / Q000187:drug effects / Q000502:physiology; D018922:HL-60 Cells; D006801:Humans; D009842:Oligopeptides / Q000502:physiology*; D018847:Opioid Peptides / Q000494:pharmacology / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D009842:Oligopeptides; D018847:Opioid Peptides; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C105293:endomorphin 1; C105294:endomorphin 2