Naltrexone partially blocks apoptosis

[Guest guest]

" The effects of DAMGO, morphine, and etorphine on apoptosis/necrosis

were not fully blocked by concomitant administration of naloxone. "

The study by Zagon (below) is important because it suggests that

naltrexone in relatively low doses, partially blocks apoptosis

(Apoptosis=programmed cell death), by certain drugs in cancer cells.

We now know that the Australians have said MS involves apoptosis of

neuronal cells. This study provides a plausible justification as to

how LDN might work (i.e. by preventing apoptosis). I occasionally

correspond with Zagon, will check with him to see what he has to say.

Yash

Zagon IS. McLaughlin PJ.

Institution

Department of Neuroscience and Anatomy, The Milton S. Hershey

Medical Center, The Pennsylvania State University, College of

Medicine, 500 University Drive, H-109, Hershey, PA 17033, USA.

iszl@...

Title

Opioids and the apoptotic pathway in human cancer cells.

Source

Neuropeptides. 37(2):79-88, 2003 Apr.

Local Messages

Hardin Library has issues up through 1999

Abstract

This study was designed to examine the role of opioids in cell

survival, with an emphasis on the mechanism of opioid growth factor

(OGF, [Met(5)]-enkephalin)-dependent growth inhibition. Using three

human cancer cell lines: MIA PaCa-2 pancreatic adenocarcinoma, HT-29

colon adenocarcinoma, and CAL-27 squamous cell carcinoma of the head

and neck, and OGF and the opioid antagonist naltrexone (NTX) at a

dosage (10(-6)M) selected because it is known to repress or

increase, respectively, cell replication, the effects on apoptosis

(TUNEL, Annexin V) and necrosis (trypan blue) were investigated on

days 2, 5, and 7 of exposure. In addition, the influence of a

variety of other natural and synthetic opioids on apoptosis and

necrosis was examined at a dosage of 10(-6)M. OGF, NTX, naloxone, [D-

Pen(2,5)]-enkephalin, [Leu(5)]-enkephalin, dynorphin A1-8, beta-

endorphin, endomorphin-1 and -2, and methadone at concentrations of

10(-6)M did not alter cell viability of any cancer cell line.

Exposure of cultures to [D-Ala(2),MePhe(4),Glycol(5)]-enkephalin

(DAMGO), morphine, or etorphine at 10(-6)M significantly increased

the number of adherent cells positively stained for TUNEL and

Annexin V, as well as the number of necrotic cells in the

supernatant, from control levels at all time points studied. The

effects of DAMGO, morphine, and etorphine on apoptosis/necrosis were

not fully blocked by concomitant administration of naloxone. Despite

the increase in cell death in some opioid-treated groups, the number

of apoptotic and necrotic adherent cells, and the number of necrotic

cells in the supernatant, was no more than 1-2% of the total cell

population. These results indicate that the inhibitory (OGF) or

stimulatory (NTX) action on cell growth in tissue culture is not due

to alterations in apoptotic or necrotic pathways. Moreover, although

some opioids increased cell death, and dose-effect relationships

need to be established, this activity was not of great magnitude and

supports the previously reported lack of growth inhibition of many

of these compounds.