Cancer Therapy: A Possible New Approach

Szent‐Györgyi, Albert; Hegyeli, Andrew F.; McLaughlin, Jane A.

doi:10.1126/science.140.3574.1391

Cited by 60 publications

(9 citation statements)

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“…The existence of a number of growth inhibitors has been postulated (1,2), and growth-inhibitory fractions have been obtained from various mammalian cells and tissues (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). Nevertheless, there are doubts as to the significance of endogenous growth inhibitors because most of the inhibitor preparations have low specific activity, the inhibitors have been difficult to purify, and with some preparations the causes of growth inhibition have, at least in part, turned out to be trivial (15)(16)(17).…”

mentioning

confidence: 99%

Purification of kidney epithelial cell growth inhibitors.

Holley¹,

Bőhlen²,

Fava³

et al. 1980

Proc. Natl. Acad. Sci. U.S.A.

154

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Two high molecular weight growth inhibitors have been isolated from the culture medium of BSC-1 cells, epithelial cells of African green monkey kidney. The purified kidney epithelial cell growth inhibitors, at ng/ml concentrations, reversibly arrest the growth of BSC-1 cells in the GI phase of the cell cycle. Their action is selective; they are most active on BSC-1 cells, are less active as inhibitors of the growth of rat lung and human breast epithelial cells, and do not inhibit the growth of 3T3 mouse embryo fibroblasts and human skin fibroblasts in culture. Their growth inhibitory action on BSC-1 cell cultures is counteracted by epidermal growth factor or calf serum.One of the areas of ignorance that remains in our broad understanding of the control of growth of mammalian cells is the subject of endogenous growth inhibitors. The existence of a number of growth inhibitors has been postulated (1, 2), and growth-inhibitory fractions have been obtained from various mammalian cells and tissues (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). Nevertheless, there are doubts as to the significance of endogenous growth inhibitors because most of the inhibitor preparations have low specific activity, the inhibitors have been difficult to purify, and with some preparations the causes of growth inhibition have, at least in part, turned out to be trivial (15-17). There is no doubt that highly active growth inhibitors exist for mammalian cells, because interferon and corticotropin are extremely active as growth inhibitors in certain cell cultures (18,19), but the inhibitory activities of these two substances could be incidental to their other biological activities. Because of the potential significance of growth inhibitors and because purified inhibitors could be very useful in the manipulation of growth of mammalian cells, we have undertaken further studies in this area.Density-dependent regulation of growth of BSC-1 cells (African green monkey kidney epithelial cells) has been found to result in part from the accumulation of growth inhibitors in the culture medium (20). The present paper describes the isolation of high molecular weight growth inhibitors from the culture medium of these cells. The growth inhibitors have very high specific activities, approximately equal to the specific activities of interferon and corticotropin in their respective cell culture assays. The new growth inhibitors appear to be selective in the types of cells on which they act. MATERIALS AND METHODSCell Cultures. BSC-1 cell stock cultures were maintained as previously described (21) in Dulbecco's modified Eagle's medium (DME medium) (22) Preparation of Conditioned Medium. Dense BSC-1 cell cultures, used for preparation of conditioned medium, were grown in 15-cm Falcon tissue culture plates in DME medium with 1% calf serum. The medium was changed once a week until the cells reached a density of approximately 1.5 X 105 cells per cm2. The cultures were then maintained in DME medium with 0.1% calf serum. To prepare conditioned medium, the cultu...

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confidence: 99%

Purification of kidney epithelial cell growth inhibitors.

Holley¹,

Bőhlen²,

Fava³

et al. 1980

Proc. Natl. Acad. Sci. U.S.A.

154

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“…Albert Szent-Györgyi, recipient of a Nobel Prize for the discovery of vitamin C, proposed that the conflict of methylglyoxal and Glo1 controlled cell growth and could be exploited for treatment of cancer. Methylglyoxal was hypothesized to be a growth-retarding substance or 'retine' and Glo1 a counter to this growth restriction effect or 'promine' [16]. The discovery of many other growth factors and change of cell responsiveness to them on malignant transformation led to the redundancy and demise of this hypothesis.…”

Section: Emergence Of Characteristics and Physiological Function Of Tmentioning

confidence: 98%

“…Gowland-Hopkins & Morgan, 1945 [12]; Racker, 1951 [13]; Racker, 1954 [14]; Szent-Gyorgyi et al, 1963 [16]; Vince & Wadd, 1969 [17]; Cooper & Anderson, 1970 [29]; Lo & Thornalley, 1992 [34]; Landro et al, 1992 [23]; Phillips & Thornalley, 1993 [30]; Cameron et al, 1997 [24]; Cameron et al, 1999 [25]; Sakamoto et al, 2000 [51]; Thornalley, 2003 [33]; Redon et al, 2006 [52]; Morcos et al, 2008 [50]; Santarius et al, 2010 [38].…”

Section: Glyoxalase In Health and Diseasementioning

confidence: 99%

“…Physiological functions proposed for the glyoxalase system have been: control of cell growth [16], glycolytic bypass in microbial systems [29], defence against dicarbonyls absorbed from gastrointestinal bacteria [31], regulation of microtubule assembly [32], and enzymatic defence against dicarbonyl glycation [33]. The last function is the one that now seems secure.…”

Section: Emergence Of Characteristics and Physiological Function Of Tmentioning

confidence: 99%

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Glyoxalase Centennial conference: introduction, history of research on the glyoxalase system and future prospects

Rabbani

Thornalley

2014

Biochemical Society Transactions

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On 27-29 November 2013, researchers gathered at the University of Warwick, Coventry, U.K., to celebrate the centennial of the discovery of the glyoxalase pathway. The glyoxalase system was discovered and reported in papers by Carl Neuberg and by Henry Drysdale Dakin and Harold Ward Dudley in 1913. All three were leading extraordinary investigators in the pioneering years of biochemistry. Neuberg proposed glyoxalase as the pathway of mainstream glycolysis and Gustav Embden correctly discounted this, later confirmed by Otto Meyerhof. Albert Szent-Györgyi proposed glyoxalase I as the regulator of cell growth and others discounted this. In the meantime, molecular, structural and mechanistic properties of the enzymatic components of the system, glyoxalase I and glyoxalase II, have been characterized. The physiological function of the glyoxalase pathway of enzymatic defence against dicarbonyl glycation, particularly by endogenous methylglyoxal, now seems secure. We are now in an era of investigation of the regulation of the glyoxalase system where a role in aging and disease, physiological stress and drug resistance and development of healthier foods and new pharmaceuticals is emerging. The history of glyoxalase research illustrates the scientific process of hypothesis proposal, testing and rejection or acceptance with further investigation, standing testament to the need for intuition guided by experience and expertise, as well as indefatigable experimentation.

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“…Some of these have been Idrived from embryos (1)(2)(3)(4), while others have originated from adult cells, or tissue components (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). During studies of protein synthesis in chick embryos, we encountered previously undescribed lowmolecular weight inhibitors of protein synthesis.…”

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confidence: 96%