• Journal of Microbiology and Biotechnology
• /
• v.14 no.5
• /
• pp.978-984
• /
• 2004

In the course of screening for a novel inhibitor of CDC2, HY558-1 was isolated from a culture broth of Penicillium minioluteum F558. Moreover, it was found that HY558-1 had an effect on both the cell cycle regulation and apoptosis of human cervical adenocarcinoma HeLa cells. A flow cytometric analysis of HeLa cells revealed appreciable cell cycle arrest at the G1 and G2/M phases following treatment with HY558-1. Furthermore, DNA fragmentation due to apoptosis was observed in HeLa cells treated with HY558-1. To obtain further information on the cell cycle arrest and apoptotic induction induced by HY558-1, the expression of certain cell cycle and apoptosis-associated proteins was examined using a Western blot analysis. The results revealed that HY558-1 inhibited the phosphorylation of pRb and decreased the expression levels of CDK2, CDC2, and cyclin A in the cell cycle progression. It was also shown that the level of $p21^{WAF1/CIP1}$ was increased in HeLa cells treated with 0.52 mM of HY558-1. Accordingly, HY558-1 was found to inhibit the proliferation of HeLa cells through the induction of G1 phase arrest by inhibiting pRb phosphorylation via an upregulation of $p21^{WAF1/CIP1}$, and G2/M phase arrest by directly inhibiting CDC2 and cyclin A. Moreover, HeLa cells treated with 0.52 mM of HY558-1 exhibited apoptotic induction associated with the cleavage of Bid and release of cytochrome c from mitochondria into the cytosol. Subsequent investigation of the activation of caspase-3 and cleavage of poly (ADP-ribose) polymerase (PARP) suggested that the mitochondrial pathway was primarily involved in the HY558-1-induced apoptosis in HeLa cells.

• Journal of Microbiology and Biotechnology
• /
• v.12 no.3
• /
• pp.470-475
• /
• 2002

In the course of screening for a novel cell cycle inhibitor, a potent Cdk 1 inhibitor, HY558, was found from the culture broth of Penicillium minioluteum F558 isolated from a soil sample. The molecular ion of HY558 was identified at m/z 329 (MH+) with a molecular formula of $C_20H_44ON_2$. HY558 exhibited selective antiproliferative effects on various human cancer cell lines. Its $IC_50$ values were estimated to be 0.29 mM on HepG2, 0.30 mM on HeLa, 0.30 mM on HL6O, 0.33 mM on HT-29, and 0.25 mM on AGS cells. Interestingly, Hy558 demonstrated no antiproliferative effect with normal lymphocytes used as the control, and a low level of inhibition on the proliferation of A549 cancer cells. A flow cytometric analysis of HepG2 cells revealed an appreciable arrest of cells at the G1 and G2/M phases of the cell cycle following treatment with Hy558. furthermore, DNA fragmentation due to apoptosis was observed in HeLa cells treated with 0.46 mM of HY558.

• The Korean Journal of Pesticide Science
• /
• v.7 no.1
• /
• pp.58-65
• /
• 2003

Various physicochemical parameters for the active ingredients of 245 herbicides were calculated to develope a diagnosis and estimation system for utility as herbicide. The range of physico-chemical parameters for each inhibitors of photo system II (H1), acetolactate synthase (ALS) (H2) and herbicides were confirmed. The distribution ranges of 85% dependence for each physicochemical parameters were Obs.logP :$-0.90\sim4.50$, dipol moment: $1.80\sim12.22$ (debye), molecular refractivity: $53.0\sim104.0(cm^3/mol)$, polarizability: $19.0\sim37.0(\AA^3)$, HOMO energy: $-9.98\sim-7.34$ (eV), LUMO energy:$-2.76\sim0.40$ (eV), Van der Waals molecular volumes: $558.0\sim995.0(cm^3)$, molecular weight: $202.0\sim430.0$ (amu) and surface areas (Grids): $194.0\sim356.0(\AA^2)$, hydration energy: $-10.16\sim114.7$ Kcal/mol, respectively. It is suggested that MR and polarizability constants will be able to distinguish between herbicides and medicinal drugs. Results revealed that various compounds based on the range of physicochemical parameters of herbicides could be diagnosed and estimated.

• Korean Journal of Microbiology
• /
• v.30 no.6
• /
• pp.558-563
• /
• 1992

Chlorobium liimicola f. thiosulfatophilum NCIB 8327 was grown on modified Pfennig's medium using ammonium chloride. glutamine. glutamate, or dinitrogen gas as nitrogen sources. Except for the case of dinitrogen gas. the extent of gro\\1h was almost the s~me. The specific activity of glutamine synthetase in crude extracts is the highest in the cells which were grown on the medium containing glutamate. hut that of glutamate synthase is uniform for all four nitrogen sources. When the concentration of ammonium ions increases in the reaction mixture. the specific activity of glutamine synthetase in crude extract from the cells grown on glutamate decreases. hut that of glutamate dehydrogenase increases. whereas that of glutamate synthase remains unchanged. When the concentration of methionine sulfoximine increases, the activity of glutamine synthetases decreases rapidly. On the other hand. when the concentration of ammonium ions increases in the reaction mixture gradually. the activity of glutamine synthetase from the cells grown on higher concentration of ammonium ions less decreases. In the presence of light. the activity of glutamine synthetase increases. hut in the dark it decreases gradually. The production of hydrogen in intact cells depends on light. It is inhihited by adding ammonium ions. hut restores immediately hy adding methionine sulfoximine. The produclion of hydrogen in this strain can he mediated by nitrogenase only. and regulated hy glutamine synthetase.