Revisiting Szent-Györgyi's Cancer Hypothesis

Mapping Intimacies ◽

10.21203/rs.3.rs-754303/v1 ◽

2021 ◽

Author(s):

Morris Alfred Johnson ◽

Michael Smits

Keyword(s):

Cell Lines ◽

Strong Interaction ◽

Human Cancer ◽

Glyoxalase I ◽

Human Cancer Cell ◽

Normal Cells ◽

Human Cancer Cell Lines ◽

Mouse Lymphoma Cells ◽

Near Term ◽

Mouse Lymphoma

Abstract Rationale for this communication • -The promine/retine hypothesis on the control of cancer never reached a definite conclusion.• -The chemical natures of promine and retine remain unsettled though usually assumed to be glyoxalases and methylglyoxal.• -Many years ago we published some data that indicated the hypothesis may be operating in plants in which glyoxalase I may exist in normal cells in an inhibited state rather than compartmentalized as in early versions of the hypothesis.• -Manju Ray in India has published many papers claiming that methylglyoxal can be used to successfully treat cancer in humans.• -We present here previously unpublished data that shows depriving glyoxalase I of GSH allows methylglyoxal to kill mouse lymphoma cells. During treatment of two human cancer cell lines, killing of one line was enhanced by blocking thioredoxin as well as GSH.It is hoped that what is conveyed here may reignite interest in the near term. Nuclear methodology and statistics can be found in Figure 1. The data show a strong interaction between the hypothesis and thiols. It is concluded that the hypothesis has yet to be thoroughly investigated.

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A cancer-unique glycan: de-N-acetyl polysialic acid (dPSA) linked to cell surface nucleolin depends on re-expression of the fetal polysialyltransferase ST8SIA2 gene

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-021-02099-y ◽

2021 ◽

Vol 40 (1) ◽

Author(s):

Gregory R. Moe ◽

Lindsay M. Steirer ◽

Joshua A. Lee ◽

Adarsha Shivakumar ◽

Alejandro D. Bolanos

Keyword(s):

Cell Surface ◽

Cell Lines ◽

Cancer Cell ◽

Fetal Development ◽

Blood Cells ◽

Human Cancer ◽

Polysialic Acid ◽

Human Cancer Cell ◽

Normal Cells ◽

Human Cancer Cell Lines

Abstract Background Polysialic acid (polySia) modifies six cell surface proteins in humans mainly during fetal development and some blood cells in adults. Two genes in humans, ST8SIA2 and ST8SIA4, code for polysialyltransferases that synthesize polySia. ST8SIA2 is highly expressed during fetal development and in cancer but not in adult normal human cells. ST8SIA4 is expressed in fetal and adult brain, spleen, thymus, and peripheral blood leukocytes and in cancer. We identified a derivative of polySia containing de-N-acetyl neuraminic acid residues (dPSA), which is expressed on the cell surface of human cancer cell lines and tumors but not normal cells. Methods dPSA-modified proteins in several human cancer cell lines and normal blood cells were identified using co-immunoprecipitation with anti-dPSA antibodies, mass spectroscopy and Western blot. RNAi and CRISPR were used to knockdown and knockout, respectively, the polysialyltransferase genes in human melanoma SK-MEL-28 and neuroblastoma CHP-134 cell lines, respectively, to determine the effect on production of cell surface dPSA measured by flow cytometry and fluorescence microscopy. Results We found that dPSA is linked to or associated with nucleolin, a nuclear protein reported to be on the cell surface of cancer but not normal cells. Knocking down expression of ST8SIA2 with RNAi or knocking out each gene individually and in combination using CRISPR showed that cell surface dPSA depended on expression of ST8SIA2. Conclusions The presence of dPSA specifically in a broad range of human cancers but not human adult normal cells offers novel possibilities for diagnosis, prevention and treatment targeting the dPSA antigen that appears to be cancer-specific, consistent across not only human cancers but also species, and may be an unrecognized mechanism of immune shielding.

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A cancer-unique glycan: de-N-acetyl polysialic acid (dPSA) linked to cell surface nucleolin depends on re-expression of the fetal polysialyltransferase ST8SIA2 gene

10.21203/rs.3.rs-246416/v1 ◽

2021 ◽

Author(s):

Gregory Moe ◽

Lindsay M. Steirer ◽

Joshua A. Lee ◽

Adarsha Shivakumar ◽

Alejandro D. Bolanos

Keyword(s):

Cell Surface ◽

Cell Lines ◽

Cancer Cell ◽

Fetal Development ◽

Blood Cells ◽

Human Cancer ◽

Polysialic Acid ◽

Human Cancer Cell ◽

Normal Cells ◽

Human Cancer Cell Lines

Abstract Background: Polysialic acid (PSA) modifies a few cell surface proteins in humans mainly during fetal development and some blood cells in adults. Two genes in humans, ST8SIA2 and ST8SIA4, code for polysialyltransferases that synthesize PSA. The product of ST8SIA2, STX, is highly expressed during fetal development and in many cancers but not in adult normal human cells. The product of ST8SIA4, PST1, is expressed in fetal and some adult tissues and also in many cancers. We identified a derivative of PSA containing de-N-acetyl neuraminic acid residues (dPSA), which is expressed on the cell surface of human cancer cell lines and tumors but not normal cells. Methods: dPSA-modified proteins in several human cancer cell lines and normal blood cells were identified using co-immunoprecipitation with anti-dPSA antibodies and mass spectroscopy. RNAi and CRISPR were used to knockdown and knockout, respectively, the polysialyltransferase genes in two different cell lines to determine effect on production of cell surface dPSA measured by flow cytometry and fluorescence microscopy. Results: We found that dPSA is linked to nucleolin, a nuclear protein reported to be on the cell surface of many cancers but not normal cells. Knocking down expression of ST8SIA2 with RNAi or knocking out each gene individually and in combination using CRISPR showed that cell surface dPSA depended on expression of ST8SIA2 and not ST8SIA4. Conclusions: The presence of dPSA specifically in a broad range of human cancers offers novel possibilities for targeting the dPSA antigen and synthetic pathway for detection, treatment, and prevention of cancer.

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