Met‐enkephalin induces cytolytic processes of apoptotic type in K562 human erythroid leukemia cells

Abstract

Cytolytic activity of Met-enke]~halin, an endogenous --17 opioid peptide, was studied within the 10--10 M concentration range in K562 human erythroid leukemia cells. Cytolytic activity was determined by the trypan blue inclusion method after 13, 15 and 18 h of Met-enkephalin co-incubation with target cells. Discrete maxima of cytolytic activity were detected at concentrations of 10-9-10 -1°, 10 -13 and 10 -aS M. Cytolysis was accompanied by internucleosomal DNA fragmentation which is indicative of the mechanism of cell death being apoptosis.

LVV‐ and VV‐hemorphins: comparative levels in rat tissues

“…However, the overall content of hemorphins in lung, heart and brain tissues, as seen from Table 1, is approximately, 3–70 nmol/g compared to 0.02–0.2 nmol/g in the case of Leu‐enkephalin in brain [26]. Since members of the hemorphin family have been shown to induce cytotoxicity and to decrease proliferation of tumor cells at very low concentrations (10 −6 –10 −13 M) [18], as compared with the concentrations needed for manifesting the opioid effects, the content of less abundant hemorphins in tissues might be quite sufficient for inducing of cytotoxic and antiproliferative effects, characteristic for `classical' ligands of opioid receptors [27]or the opioid‐like peptides casomorphins [28].…”

Opioids As Modulators of Cell Death and Survival—Unraveling Mechanisms and Revealing New Indications

“…The latter effect was shared by Met-enkephalin and inhibited with the DOR-specific antagonist naltrindole (Shahabi et al, 1996), indicating that this effect was probably mediated through the ␦ receptor. Met-enkephalin also stimulated T-cell proliferation (Singh et al, 1999) probably by activating Erk-signaling pathways (Sharp et al, 1998b;Shahabi et al, 1999;Kramer et al, 2002); however, it induced apoptosis in leukemia cells (Mernenko et al, 1996). Dynorphin A, a specific KOR agonist (Chavkin et al, 1982), enhanced the mitogen-induced proliferative response and interleukin-2 production of rat splenocytes.…”

Cytotoxic activity of acetylcholine receptor ligands

“…It was shown earlier that Met-enkephalin [12], TNF [t4], neokyotorphin fragment 1-4 (TSKY) [18], substance P (SP) [4] and valorphin [13] exhibited very similar effects, so this phenomenon is general for ligands of several receptor systems, in [5]. These data allow to propose that the ability to induce several cytolytic processes is a general feature of a number of receptor-active substances.…”

“…Since NT II preparations might contain cytotoxic enzymes from snake venom, the peptide was purified additionally. exhibited by Mct-enkephalin [ 12], valorphin [ 13 ] and tumor necrosis factor (TNF) [14] was detected at concentrations significantly lower than corresponding binding constants determined by radio-ligand method.…”