Stimulation of sterol and DNA synthesis in leukemic blood cells by low concentrations of phytohemagglutinin

Chen, H.W.; Heiniger, H J; Kandutsch, Andrew A.

doi:10.1016/0014-4827(77)90004-0

Cited by 21 publications

(3 citation statements)

References 23 publications

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“…On the other hand, 7-keto-cholesterol is reported to induce apoptosis in several cell lines such as smooth muscle cells [13] and vascular smooth muscle cells [14] by an as-yet unknown mechanism. In addition, the inhibition of sterol biosynthesis, through the inhibition of the 3-hydroxy-3-methylglutaryl co-enzyme A reductase, is reported to give oxysterols an antiproliferative activity [4], both in in vivo and in in vitro studies [15][16][17], even including leukemic blood cells [18].…”

Section: Introductionmentioning

confidence: 99%

The allylic 7-ketone at the steroidal skeleton is crucial for the antileukemic potency of chlorambucil’s active metabolite steroidal esters

et al. 2004

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We have investigated the role of the allylic 7-ketone in oxidized Delta5-steroids on antileukemic activity. We synthesized and studied a series of oxidized and non-oxidized steroidal esters of p-N,N-bis(2-chloroethyl)aminophenylacetic acid (PHE), chlorambucil's active metabolite. In a comparative study of these 7-keto derivatives, on a molecular basis, regarding their ability to induce sister chromatid exchanges (SCEs) and to inhibit cell proliferation in normal human lymphocytes in vitro, the results with these 7-keto derivatives, on a molecular basis, correlated well with their antileukemic potency against leukemia P388- and L1210-bearing mice, which proved to be significantly increased compared to that of the non-oxidized derivatives. Our results indicate that the role of the steroidal skeleton it is not only for the transportation of the alkylating agent into the cell, but also contributes directly to the mechanism of antileukemic action, by an as-yet unknown way. The main conclusion from this study is that the existence of the allylic 7-keto group in the skeleton of the Delta5-steroidal esters impressively enhances their antileukemic activity, while the toxicity remains at clinically acceptable levels, suggesting that this structural modification should be further investigated.

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Section: Introductionmentioning

confidence: 99%

The allylic 7-ketone at the steroidal skeleton is crucial for the antileukemic potency of chlorambucil’s active metabolite steroidal esters

et al. 2004

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“…The lipid composition of the plasma membrane can be modified experimentally through, for example, cholesterol depletion [15][16][17][18][19][20], or accumulation [21]; modification of the polar head-groups of the phospholipids [22][23][24], or modification of the fatty acid composition [25][26][27][28][29][30]. A change in phospholipid composition upon supplementation with stearic acid, oleic acid or linoleic acid has been described in neuroblastoma x glioma hybrid cells [29] and other cell lines [31,32].…”

Section: Introductionmentioning

confidence: 99%

Effect of fatty acids on plasma membrane lipid dynamics and cation permeability in neuroblastoma cells

Boonstra

Nelemans

Feijen

et al. 1982

Biochimica et Biophysica Acta (BBA) - Biomembranes

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In this study the effects of experimental modifications of plasma membrane lipid lateral mobility on the electrical membrane properties and cation transport of mouse neuroblastoma cells, clone Neuro-2A, have been studied. Short-term supplementation of a chemically defined growth medium with oleic acid or linoleic acid resulted in an increase in the lateral mobility of lipids as inferred from fluorescence recovery after photobleaching of the lipid probe 3,3'-dioctadecylindocarbocyanide iodide. These changes were accompanied by a marked depolarization of the membrane potential from -51 mV to -36 mV, 1.5 h after addition, followed by a slow repolarization. Tracer flux studies, using S6Rb÷ as a radioactive tracer for K ÷ , demonstrated that the depolarization was not caused by changes in (Na ÷ + K + )-ATPase-mediated K + influx or in the transmembrane K ÷ gradient. The permeability ratio (PNa/PK), determined from electrophysiological measurements, however, increased from 0.10 to 0.27 upon supplementation with oleic acid or linoleic acid. This transient rise of PN,/Px Was shown by 24Na+ and S6Rb+ flux measurements to be due to both an increase of the Na + permeability and a decrease of the K ÷ permeability. None of these effects occurred upon supplementation of the growth medium with stearic acid.

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“…In order to maintain the cells in a state of balanced growth, it is necessary to couple DNA synthesis and membrane lipid synthesis [12]. It has been reported that cholesterol biosynthesis is a prerequisite for DNA synthesis in in vitro-propagated cells [13] and that DNA synthesis is inhibited when cholesterol synthesis is blocked [ 12,141. Thus insulin and dexamethasone are probably playing dual roles in the support of growth of PA-III/: ie, mitogenic and stimulatory to the cholesterol biosynthesis.…”

Section: Discussionmentioning

confidence: 99%

A chemically defined medium for the propagation of rat prostate adenocarcinoma cells

Chan

1981

The Prostate

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A chemically defined medium (MB-DF) has been developed for the propagation of the rat prostate adenocarcinoma cell line (PA-III). The medium (MB-DF) was supplemented with fetuin, insulin, transferrin, dexamethasone, and 5 alpha - dihydrotestosterone, but require no serum supplement. The adapted line, PA-IIIf, has been grown in this serum-free medium for 30 passages over a period of 12 months without losing the malignant or other characteristics of the parent line. When transplanted into syngeneic rats, the PA-IIIf cells reconstituted the adenocarcinoma and metastasized spontaneously via ipsilateral lymphatic channels to the lungs. This cell line will be of use in further analyses of enzymes associated with biological properties of the tumor cells.

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Stimulation of sterol and DNA synthesis in leukemic blood cells by low concentrations of phytohemagglutinin

Cited by 21 publications

References 23 publications

The allylic 7-ketone at the steroidal skeleton is crucial for the antileukemic potency of chlorambucil’s active metabolite steroidal esters

The allylic 7-ketone at the steroidal skeleton is crucial for the antileukemic potency of chlorambucil’s active metabolite steroidal esters

Effect of fatty acids on plasma membrane lipid dynamics and cation permeability in neuroblastoma cells

A chemically defined medium for the propagation of rat prostate adenocarcinoma cells

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