Rapamycin (AY-22,989), a new antifungal antibiotic. IV. Mechanism of action.

Singh, Kartar; Sun, Sheila; Vézina, Claude

doi:10.7164/antibiotics.32.630

Cited by 94 publications

(53 citation statements)

References 3 publications

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“…Acu appeared to inhibit synthesis of mannan to some extent, in addition to the synthesis of alkali-insoluble p-glucan. This finding is in agreement with reports by Mizoguchi et al (1977), Singh et al (1979 and Yamaguchi et al (1982) who worked with Saccharomyces cerevisiae, Candida albicans AY F-598 and C . albicans MTU 12077, respectively.…”

Section: Discussionsupporting

confidence: 93%

Morphological Alterations of the Fission Yeast Schizosaccharomyces pombe in the Presence of Aculeacin A: Spherical Wall Formation

1985

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The fission yeast Schizosaccharomyces pombe, grown in the presence of aculeacin A (Acu), an antifungal antibiotic, forms spherical rather than cylindrical walls. This aberrant morphogenesis was studied in the presence of Acu at 1 pg ml-l under conditions in which over 90% of the cells continued to grow but with altered morphology. Microscopic observations and chemical analyses revealed that the spherical walls had a looser structure than the cylindrical wall and that their syntheses of alkali-insoluble glucan and mannan were reduced whereas the synthesis of alkali-soluble glucan was enhanced. Spherical walls of glutaraldehyde-fixed cells were hardly digested by Zymolyase 60000 [a (1+3)-P-glucanase] but were digested by Novozym 234 [a (1+3)-a-glucanase]. From these results the components and morphology of the spherical walls are discussed in comparison with the cylindrical walls.

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Section: Discussionsupporting

confidence: 93%

Morphological Alterations of the Fission Yeast Schizosaccharomyces pombe in the Presence of Aculeacin A: Spherical Wall Formation

1985

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“…cancer drug [90,91]. Nevertheless, rapamycin has limited bioavailability due to its poor aqueous solubility.…”

Section: Rapamycin and Its Derivativesmentioning

confidence: 99%

Metformin and mTOR Inhibitors: Allies against Ovarian and Breast Cancers

Guimarães¹,

Tessarollo²,

Santos³

et al. 2017

J Carcinog Mutagen

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Cancer is one of the leading causes of death worldwide. Every year 8.2 million people die from the disease. In this context, breast and ovarian cancer are the most incidental among women. Elucidation of cell growth pathways and the observation that these pathways are altered in human cancer have encouraged the search for specific inhibitors. The phosphatidylinositol-3cinase (PI3K)/Protein kinase b (AKT)/Mammalian Target of Rapamycin (mTOR) is an important pathway involved in cell growth, tumorigenesis, cell invasion, and resistance to therapies. This pathway is often activated in breast and ovarian cancers and the deregulation of its signaling can contribute to tumor growth, angiogenesis and metastasis. Metformin is one of the most commonly prescribed antidiabetic drugs in the world whose anticancer effects, mediated by reduced mTOR signaling, have become notable. Therefore, this review provides an overview of signaling pathway PI3K/AKT/mTOR in the ovarian and breast cancers as well as for target therapies of mTOR signaling, with an emphasis on its mechanisms, clinical applicability and future perspectives.

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“…Early studies showing reduced fungal amino acid, nucleic acid, and lipid metabolism after rapamycin treatment have linked TOR to metabolic functions (Singh et al 1979). Later transcription profiling screening of lymphoma cells treated with rapamycin revealed a tendency towards catabolism and that the levels of many mRNA involved in lipid, nucleotide, and protein synthesis were downregulated (Peng et al 2002).…”

Section: Metabolismmentioning

confidence: 99%