Cell cycle arrest and antitumor activity of pironetin and its derivatives

Kondoh, Masuo; Usui, Takeo; Kobayashi, Shinichi; Tsuchiya, Kouichi; Nishikawa, Kiyohiro; Nishikiori, Takaaki; Mayumi, Tadanori; Osada, Hiroyuki

doi:10.1016/s0304-3835(97)00528-4

Cited by 93 publications

(50 citation statements)

References 11 publications

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“…4B). Treatment with pironetin, a tubulin binder, 13,45) of HepG2-Bcl-2 cells led to Bcl-2 phosphorylation at Ser-70 and Ser-87 residues, and enhanced sensitivities to other antitumor compounds (data not shown). These observations indicate that phosphorylation of Bcl-2 results in the inactivation of anti-apoptotic function and thus are consistent with some previous reports.…”

Section: Discussionmentioning

confidence: 97%

Dephosphorylation of Bcl‐2 by protein phosphatase 2A results in apoptosis resistance

Simizu¹,

Tamura²,

Osada³

2004

Cancer Science

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Section: Discussionmentioning

confidence: 97%

Dephosphorylation of Bcl‐2 by protein phosphatase 2A results in apoptosis resistance

Simizu¹,

Tamura²,

Osada³

2004

Cancer Science

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“…A wide range of bioactivities such as plant growth-regulating [2,3], antitumour [4,5], antimicrobial and antifungal activities [6,7] have demonstrated the medicinal importance of 2-pyrones. In our search for new bioactive compounds from the marine-derived fungus Aspergillus flavus c-f-3 separated from a marine algae sample collected in Putian Pinghai, China, two new 5-hydroxy-2-pyrone derivatives (1, 2) were isolated.…”

Section: Introductionmentioning

confidence: 99%

Two New 5-Hydroxy-2-pyrone Derivatives Isolated from a Marine-derived Fungus Aspergillus flavus

Lin

Fang

et al. 2008

J Antibiot

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Two new compounds, 4-(hydroxymethyl)-5-hydroxy-2H-pyran-2-one (1) and (5-hydroxy-2-oxo-2H-pyran-4-yl) methyl acetate (2), have been isolated from a marine-derived fungus Aspergillus flavus. Their structures were determined by spectroscopic data. Compound 1 induced the production of cAMP on GPR12 transfected CHO and HEK293 cells in a dose-dependent manner, which indicated 1 might be a possible ligand for GPR12.Keywords marine-derived fungus, Aspergillus flavus, 5-hydroxy-2-pyrone, cAMP, GPR12 Introduction 2-Pyrone is a six-membered cyclic unsaturated ester, which is highly abundant in bacteria, microbial, plant, insect and animal systems and takes part in many different types of biological processes such as defence against other organisms, as key biosynthetic intermediates, and as metabolites [1]. A wide range of bioactivities such as plant growth-regulating [2,3], antitumour [4,5], antimicrobial and antifungal activities [6,7] have demonstrated the medicinal importance of 2-pyrones. In our search for new bioactive compounds from the marine-derived fungus Aspergillus flavus c-f-3 separated from a marine algae sample collected in Putian Pinghai, China, two new 5-hydroxy-2-pyrone derivatives (1, 2) were isolated. The biological activities of 1 and 2 were tested using cAMP assay in GPR12 transfected CHO and HEK293 cells. In this paper we described the isolation and structure elucidation of 1 and 2 (Fig. 1) as well as their bioactivities. Materials and Methods MicroorganismThe Aspergillus flavus c-f-3 was separated from a marine algae Enteromorpha tubulosa, collected at Putian Pinghai, China, in August, 2005, using dilution-plate method [8] on PDA medium [9]. It was identified according to its morphological characteristic by Prof. Hong Kui (the Chinese Academy of Tropical Agricultural Sciences, Hainan, China). Working stocks were prepared on Potato Dextrose agar slants stored at 4°C. Two New 5-Hydroxy-2-pyrone Derivatives Isolated from a Marine-derived Fungus

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“…as described previously. 31,32) Vinblastine sulfate was purchased from Wako Pure Chemical Industries, Ltd. (Osaka). Paclitaxel, camptothecin, etoposide, adriamycin and cyclosporin A were obtained from Sigma (St. Louis, MO).…”

Section: Methodsmentioning

confidence: 99%

Bcl‐2 Inhibits Calcineurin‐mediated Fas Ligand Expression in Antitumor Drug‐treated Baby Hamster Kidney Cells

Simizu

Shibasaki

Osada

2000

Japanese Journal of Cancer Research

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It is well known that human leukemia cells, such as HL-60 and U937 are sensitive to antitumor drugs, but human normal lung fibroblasts, such as WI-38 cells are resistant to the drugs. However, the mechanisms of the different responses to apoptosis in these cell lines remain unclear. We report here that an increase of Fas and Fas ligand (FasL) expression was required for antitumor druginduced apoptosis in WI-38 and baby hamster kidney (BHK) cells, but not in HL-60 cells. Then, we used BHK cells transfected with the bcl-2 gene to investigate the involvement of complex formation of Bcl-2 and calcineurin. Calcineurin was imported to the nucleus in response to the drug treatment. Overexpression of Bcl-2 and cyclosporin A treatment inhibited the nuclear import and FasL expression, and as a result, both inhibited apoptosis. Although a caspase inhibitor, z-Asp-CH 2 -DCB, suppressed the drug-induced apoptosis, it failed to inhibit the drug-induced expression of Fas and FasL. These findings suggest that initially the Fas/FasL system is activated by calcineurindependent transcription followed by activation of the downstream caspase cascade resulting in antitumor drug-induced apoptosis in BHK cells, but not in HL-60 cells. Furthermore, Bcl-2 inhibits the nuclear import of calcineurin and suppresses calcineurin-mediated FasL expression during antitumor drug-induced apoptosis.

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Cell cycle arrest and antitumor activity of pironetin and its derivatives

Cited by 93 publications

References 11 publications

Dephosphorylation of Bcl‐2 by protein phosphatase 2A results in apoptosis resistance

Dephosphorylation of Bcl‐2 by protein phosphatase 2A results in apoptosis resistance

Two New 5-Hydroxy-2-pyrone Derivatives Isolated from a Marine-derived Fungus Aspergillus flavus

Bcl‐2 Inhibits Calcineurin‐mediated Fas Ligand Expression in Antitumor Drug‐treated Baby Hamster Kidney Cells

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