Welcome to the NTI research library. This section contains a rich collection of information about our products and the associated research. Click on the subject line to read more. Subscribe to our e-newsletter to receive updates on products and research.
Effects of Phosphoglycolipid Extract (NT
FACTOR)
on Normal and Cancerous Cells
David S. Newburg, Ph.D.
Director, Program in Glycobiology
Cancerous cells of tumors import phospholipids from normal
cells.
One of the fundamental biochemical differences between
tumor cells and normal cells is the composition of the membrane lipid, including
glycosphingolipid and phospholipids. The phospholipid content of tumor cell
membranes in known to be distinct from that of normal cells (Bergelson 1974,
Spangler 1975, Hostetler 1976, Burlakova 1980, 1991). The difference in
phospholipid content has been attributed to differences in rates of phospholipid
transfer to the plasma membrane of aggressive tumors. There are two components
to this difference in the ability of tumor membranes to acquire phospholipids
from neighboring cells: first is a difference in phospholipid exchange due to
phospholipid exchange protein (PLEP); second is a difference in phospholipid
exchange rates due to the intrinsic lipid composition of the membrane. Over 90%
of the Phosphatidylcholine in hepatoma microsomes can be exchanged within two
hours at 370C (Palmina 1995). In Morris hepatoma cells, the transfer
activity of phosphatidylcholine was 2 to 3 times higher than in controls (Poorthuis
1980). However, only some of this difference could be accounted for by an
increase in PLEP activity, the rest being attributed to intrinsic differences in
membrane lipids. Clearly, many types of tumors are able to incorporate
extrinsic phospholipids into their membranes at the expense of normal cells of
the body with the potential to deplete the phospholipids in the normal cells.
Reduced levels of
phospholipids in normal cells can limit metabolic activity and limit available
energy.
Phospholipids, as part of the membrane structure, maintain
membrane integrity, and, through changes in membrane fluidity, also regulate
enzyme activities and membrane transport processes (Spector 1981, 1985).
Phospholipids can have other specific functions. Signal transduction utilizes
phospatidylcholine and phosphatidylinositol for the production of diacyl
glycerol (DAG) by phospholipase C (Berridge 1989) and for the production of
inositol triphosphate (IP3) (Ranan 1990, Michell 1988, Margolis
1990). One of the choline phospholipids (1-alkyl-2acetyl-SN-glycerol-3-phosphocholine)
is the substrate for the synthesis of platelet activating factor (Synder 1989).
The arachidonic acid found as part of the structure of choline or inositol
phospholipid is utilized for the production of prostaglandin and leukotriene (Nordoy
1990). The choline of phosphatidylcholine may be used in neural tissue for the
synthesis of acetylcholine (Blusztain 1987).
Plasma brain and neuronal choline concentrations were
elevated by oral administration of choline, which also causes the release of
acetylcholine in the neuromuscular system (Haubrich 1976, Cohen 1976).
Furthermore, muscle function has been shown to decrease during choline
deficiency (Zeisel 1990). Physical stress depresses plasma choline
concentration, e.g., individuals in the Boston Marathon of 1986 showed 40%
decreases in plasma choline levels during the race (Conlay 1986). Providing
phosphatidylcholine prior to exercise can compensate for these choline losses
(von Allwörden1993). Even with shorter and less strenuous forms of exercise, a
supplemental supply of lecithin results in an increase in performace (von
Allwörden 1995).
When tumor cells sequester large amounts of the phosphatidylcholine produced by normal cells, this could lead to a loss of choline homeostasis, producing decreases in plasma, brain, and muscle choline that would be expected to result in muscle fatigue. This could account for some of the malaise and chronic fatigue that is known to accompany certain forms of cancer. Under these circumstances, exogenous oral supplements would be expected to provide some measure of relief from cancer-associated fatigue.
The rate of phospholipid
accumulation in cancer cells is independent of exogenous supply.
In general, adult tissues contain more phosphatidylcholine
than immature tissues (Sun 1985, Yorek 1993). Like immature developing tissues,
some tumors contain lower levels of phospholipid than corresponding normal
tissue (Bergelson 1975). However the phospholipid content varies greatly from
tumor to tumor. Many varieties of cancerous tissue contain more
phosphatidylcholine with increased amounts circulating in the blood and
available for use by the tumor (Takenaka 1983, Nikolasev 1972, Aso 1981). Thus,
some tumors can deplete normal tissue of phospholipid.
NT FactorTM phosphoglycolipid improves cell maintenance and metabolic activity of normal cells.
The integrity of mitochondria and their ability to produce
energy can be measured by isolating lymphocytes, treating them with Rhodamine
123 (a mitochondrial stain), and analyzing them using FACSCAN, a flow cytometer
modified for analysis of mitochondria. In rats, there is a measurable decrease
in mitochondrial function as the rat ages. However, in rats fed a diet that
contains NT FactorTM phosphoglycolipid, mitochondria showed a 20%
improvement over those fed the identical diet without the NT FactorTM,
as measured by Rhodamine flow cytometry. (Michael Seidman, personal
communication)
Assuming that the degradation of mitochondrial function
with age is caused by cumulative chemical toxicity, it would appear that NT
FactorTM phosphoglycolipid is able to protect normal tissue from this
type of chemical induced damage.
NT FactorTM
phosphoglycolipid contains high concentrations of lysolecithins.
When NT FactorTM phosphoglycolipid was analyzed
in our laboratory and its composition compared to that of the parent soy-derived
material from which it was extracted, we found that NT FactorTM
phosphoglycolipid contains substantially more phosphatidylcholine than the
parent material. Although the fatty acid composition of the phosphatidylcholine
from NT FactorTM phosphoglycolipid was not different from that of
the parent compound, by virtue of concentrating the phosphatidylcholine the
extraction process also concentrated polyunsatured phosphatidylcholine. The
greatest difference between the preparations was that NT FactorTM
phosphoglycolipids had over 6 times the lysolecithin content of the parent
compound. This suggests that any unique biological activity of NT FactorTM
may be due in part to its lysolecithin content, either acting alone or in
concert with other of its components.
Lysolecithin derivatives
disrupt cancer cells at concentrations that do not affect normal cells.
Lysolecithin-like molecules are selectively cytotoxic to
cancer cells in vitro (Hoffman 1986, Harmann 1986, Berger 1984). Such compounds
inhibit HL60 leukemic cells at a dosage that has no effect on normal human
marrow cells, the tissue from which the leukemic cells are derived. Normal
cells were able to tolerate 4 times higher dosage than the leukemic cells during
24 hours incubation with the phospholipid preparation (Berdel 1986). There was
up to a 5-fold difference in sensitivity between the normal and tumor cells with
breast, ovarian, and lung cancer cells, as well as with mesothelioma cells (Namba
1993).
In summary, some cancerous cells are able to deplete normal
cells of phospholipids, causing a degradation in function, and possibly leading
to lethargy. NT FactorTM phosphoglycolipid is a very rich source of
phospholipids, and also contains high levels of lysolecithin. Lysolecithin-like
molecules are able to inhibit tumors at doses that do not affect normal cells.
REFERENCES:
Aso Y, Kujita K, Tajima A, Suzuki K, Yokoyama M. (1981) Acta Urol. Jpn. 27:1345-1349.
Berdel WE, Von Hoff DD, Unger C, Schick HD, Fink U,
Reichert A, Eible H, Rastetter J. (1986) Ether lipid derivatives: Antineoplastic
activity in vitro and the structure-activity relationship. Lipids 21:301-304.
Bergelson LD, Dyatlovitskaya EV, Sorokina IV, Gorkova IB. (1974) Biochim. Biophys. Acta 360-361.
Bergelson LD, (1972) Tumor lipids. Prog. Chem. Fats Lipids
13:1
Berridge MJ. Irvine RF. (1989) Inositol phosphates and cell
signaling. Nature 341:197
Blusztain JK, Liscovitch M, Mauron C, Richardson UI,
Wurtman RJ. (1987) Phosphatidylcholine as a precursor of choline for
acetylcholine synthesis J. Neural Trans. 24:247
Bogguest WA. (1973) Adv. Tumoyur Prev. Detect. Charact (Charact.
Hum. Tumours, Proc. Int. Symp., 5th)1974: 279-289
Burlakova EB, Palmina NP, Maltseva EL. (1991) In
Vigo-Pelfrey C (ed.), Membrane Lipid Oxidation III. Boca Raton, Florida: CRC
Press, pp. 209-237
Burlakova KJ, Molochkina EM, Palmina NP. (1980) In
Weber G (ed.) Advances in Enzyme Regulation. New York: Pergamon Press, vol 15,
pp.163-179.
Cohen EL, Wurtman RJ. (1976) Science 19:561
Conlay LA, Wurtman RJ, Blusztajn K, Coviella IL, Maher TJ,
Evoniuk GE. (1986) New Engll. J. Med. 175:892
Harmann DB, Heumann HA. (1986) Cytotoxic ether
phospholipids. Different affinities to Lysophosphocholine acytransferases in
sensitive and resistant cells. J. Biol. Chem. 261:7742-7747.
Haubrich DR, Wang PF, Chippendale T, Proctor E. (1976) J.
Neurochem. 27:1305.
Hietanen E, Punnonen K, Punnonen, R, Auvinen O. (1986)
Carcinogenesis 7:1965-1969.
Hoffman DR, Hoffman LH, Synder F. (1986) Cytotoxicity and
metabolism of alkyl phopholipid analogues in neoplastic cells. Cancer Res.
46:5803-5809.
Hostetler KJ, Zenner BD, Morris HP. (1976) Biochim. Biophys,
Acta 441:231
Leung BS, Sun GY. (1976) Proc. Soc. Exp. Biol. Med. 152:
671-676.
Margolis B, Zilberstein A, Franks C, Felder S, Kremer S,
Ullrich A, Rhee SG, Skorecki K, Schlessinger J.(1990) Effect of
phospholipase-C-coverexpression on PDGF induced second messengers and
mitogenesis.
Science 248:607
Michell RH. (1998) Phosphoinositides and inositol
phosphates. Biochem. Soc. Trans. 17: 1.
Namba Y. (1993) Medical applications of phospholipid. In
Cevc G (ed.), Phospholipids Handbook. New York: Marcel Dekker, Inc., p 892.
Nikolasev V, Lazar G, Karady I. (1972) Kiserl. Orvostud.
24:465-469
Nordoy A, Goodnight SH. (1990) Dietary lipids and
thrombosis. Arteriosclerosis 10:149
Palmina NP. (1995) Phosphatidylcholine exchange in
membranes of normal and tumor tissues. In Cevc G,
Paltauf F (eds.). Phospholipids: Characterization,
Metabolism, and Novel Biological Applications.
Chamaign, Illinois: AOCS Press, pp. 311-318.
Poorthuis Ben JHM, van der Krift TP, Teerlink T, Akeroyd R,
Hjostetler KW, Wirtz KWA. (1980) Biochim.
Biophys. Acta 600:376.
Rana Rs, Hokin LE. (1990) Role of phosphoinositides in
transmembrane signaling, Phys. Rev. 70: 115.
Snyder F, Lee TC, Blank ML. (1989) Platelet activating
factor and related ether lipid mediators. Ann. NY Acad. Sci. 568:35.
Spangler M, Coetzee ML, Katyal SL, Morris HP, Ove P.
(1975) Cancer Res. 35:3131.
Spector A A, Mathur SN, Kaduce TL, Hyman BT. (1981) Lipid
nutrition and metabolism of cultured mammalian cells. Prog. Lipid Res. 19:155.
Spector AA, Yorek MA. (1985) Membrane lipid compositin and
cellular function. J. Lipid Res. 26:10105.
Sun GY, Foudin LL. (1985) Phospholipid composition and
metabolism in the developing and aging nervous System. In Eichberg J
(ed.), Phospolipids in Nervous Tissue. New York: Wiley, p. 79.
Takenaka R, Inoue M, Hori T, Okuyama H. (1983) Biochim.
Biophys. Acta 754: 28-37.
Tan W C, Chapman C, Takatori T, Privett OS, (1975) Lipids
10:70-74.
Von Allwörden HN, Horn S, Feldheim W. (1995) The influence
of lecithin on the performance and the recovery process of endurance athletes.
In Cevc G, Paltauf F (eds.) Phospholipids: Characterization, Metabolism,
and Novel Biological Applications. Champaign, Illlinois: AOCS Press, pp.
319-325.
Von Allwörden HN, Horn S, Kahl J, Feldheim W. (1993) Eur.
J. Appl. Physiol. 67: 87.
Yorek MA (1993) Biological distribution. In Cevc G
(ed.), Phospholipids Handbook. New York: Marcel Dekker, Inc., p. 760.
Zeisel SH (1990) In Hanin I, Pepeu G (eds.), Phospholipids, Biochemical, Pharmaceutical and Analytical Considerations. New York: Plenum Press, pp. 219-231.
View information about product support
Return to Library | Return to Article Top
(c) Copyright
1997-2007 Nutritional Therapeutics - Hauppauge, NY