Binding of opioids to human MCF-7 breast cancer cells and their effects on growth.
The well characterized human breast cancer cell line, MCF-7, has been shown to possess membrane receptors for various opioid ligands, and these compounds have been shown to modulate the growth of the cells in culture. Using specific radioligands for the receptor types, we were able to demonstrate that the MCF-7 cells possess multiple opioid receptor types. Relatively high-affinity-binding sites are present for the mu- and kappa-specific ligands, while lower affinity sites are present for the delta-agonist. Opioid ligands specific for the different receptor types significantly inhibited the growth of the MCF-7 cells in a dose-dependent manner when grown in the presence of 10% fetal bovine serum. This inhibitory effect was reversed by the simultaneous administration of the opioid receptor antagonist, naloxone. However, the opioid effect appears to be restricted to the hormonally responsive fraction of the MCF-7 cell growth. Cells grown in the presence of charcoal-stripped fetal bovine serum are refractory to the effects of the opioids unless the media is supplemented with estradiol. The data presented here suggest an important regulatory role for opioids in the growth and development of human breast cancers.
Maneckjee
R
R
NCI Navy Medical Onocology Branch, Bethesda Naval Hospital, Maryland 20814.
Biswas
R
R
Vonderhaar
B K
BK
D001943:Breast Neoplasms; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D003496:Cyclazocine / Q000494:pharmacology*; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D016308:Enkephalin, Leucine-2-Alanine; D004958:Estradiol / Q000494:pharmacology; D005048:Etorphine / Q000378:metabolism*; D005260:Female; D006801:Humans; D007700:Kinetics; D009019:Morphinans / Q000378:metabolism*; D009020:Morphine / Q000494:pharmacology*; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
D009019:Morphinans; D011957:Receptors, Opioid; D005048:Etorphine; D004958:Estradiol; D004743:Enkephalin, Leucine; D016308:Enkephalin, Leucine-2-Alanine; D009020:Morphine; D003496:Cyclazocine