Growth inhibition and induction of phenotypic alterations by tiazofurin: Differential effects on MCF-7 breast cancer and HBL-100 breast cell lines

Sidi, Yechezkel; Beery, Einat; Panet, C.; Wasserman, Lina; Novogrodsky, Abraham; Nordenberg, Jardena

doi:10.1016/0277-5379(89)90136-3

Cited by 12 publications

(1 citation statement)

References 12 publications

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“…In vitro activity of tiazofurin was observed against many human cancer cell lines, including leukemia, colon, lung, ovarian, renal, breast, and melanoma [104,105,106,107,108,109]. Tiazofurin induced differentiation of the human promyelocytic leukemia cell line HL60 [110] and the erythroleukemia cell line K-562 [111].…”

Section: Other Impdh Inhibitorsmentioning

confidence: 99%

Anti-Tumor Potential of IMP Dehydrogenase Inhibitors: A Century-Long Story

Naffouje

Grover

et al. 2019

Cancers

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The purine nucleotides ATP and GTP are essential precursors to DNA and RNA synthesis and fundamental for energy metabolism. Although de novo purine nucleotide biosynthesis is increased in highly proliferating cells, such as malignant tumors, it is not clear if this is merely a secondary manifestation of increased cell proliferation. Suggestive of a direct causative effect includes evidence that, in some cancer types, the rate-limiting enzyme in de novo GTP biosynthesis, inosine monophosphate dehydrogenase (IMPDH), is upregulated and that the IMPDH inhibitor, mycophenolic acid (MPA), possesses anti-tumor activity. However, historically, enthusiasm for employing IMPDH inhibitors in cancer treatment has been mitigated by their adverse effects at high treatment doses and variable response. Recent advances in our understanding of the mechanistic role of IMPDH in tumorigenesis and cancer progression, as well as the development of IMPDH inhibitors with selective actions on GTP synthesis, have prompted a reappraisal of targeting this enzyme for anti-cancer treatment. In this review, we summarize the history of IMPDH inhibitors, the development of new inhibitors as anti-cancer drugs, and future directions and strategies to overcome existing challenges.

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Section: Other Impdh Inhibitorsmentioning

confidence: 99%

Anti-Tumor Potential of IMP Dehydrogenase Inhibitors: A Century-Long Story

Naffouje

Grover

et al. 2019

Cancers

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Effects of differentiation-inducing agents on purine nucleotide metabolism in an ovarian cancer cell line

Zoref-Shani

Lavie

Bromberg

et al. 1994

J Cancer Res Clin Oncol

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The effects of the differentiation-inducing agents sodium butyrate (NaOBt), dimethylsulfoxide (DMSO) and mycophenolic acid (MA), on purine nucleotide metabolism, was studied in an ovarian carcinoma cell line (GZL-8). Exposure to these agents inhibited cell proliferation, but did not affect cell viability. Three hours following exposure, NaOBt and DMSO moderately decelerated purine synthesis de novo, but MA accelerated it three-fold, this being associated with a two-fold increase in the excretion of hypoxanthine and xanthine into the incubation medium. NaOBt and DMSO did not affect the cellular nucleotide content, but MA caused a 73% decrease in GTP content and about a 50% increase in the cellular content of UTP. The following alterations in cellular enzyme activity were observed 72 h following exposure: NaOBt decreased the activity of hypoxanthine-guanine phosphoribosyltransferase and increased the activity of IMP and of AMP 5'-nucleotidases, DMSO increased the activity of IMP 5'-nucleotidase, and MA increased the activity of the two nucleotidases. The results suggest that, in the carcinoma cell line studied, the differentiation process induced by NaOBt and DMSO may be associated with a general shift in the direction of purine metabolism from anabolism to catabolism, whereas that induced by MA is associated with a specific decrease in the production of GTP.

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Mycophenolate mofetil: Molecular mechanisms of action

Wu¹

1994

Perspectives in Drug Discovery and Design

106

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Growth inhibition and induction of phenotypic alterations by tiazofurin: Differential effects on MCF-7 breast cancer and HBL-100 breast cell lines

Cited by 12 publications

References 12 publications

Anti-Tumor Potential of IMP Dehydrogenase Inhibitors: A Century-Long Story

Anti-Tumor Potential of IMP Dehydrogenase Inhibitors: A Century-Long Story

Effects of differentiation-inducing agents on purine nucleotide metabolism in an ovarian cancer cell line

Mycophenolate mofetil: Molecular mechanisms of action

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