Re: Naltrexone partially blocks apoptosis

[Guest guest]

nice one...

> 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.

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