Five hundreds and fifty LACA mice were used in 3 batches for studying the anticarcinogenic effect of Konjaku powder on MNNG-induced lung cancers. These mice (within each batch) were randomly allocated to four groups, ...Five hundreds and fifty LACA mice were used in 3 batches for studying the anticarcinogenic effect of Konjaku powder on MNNG-induced lung cancers. These mice (within each batch) were randomly allocated to four groups, namely, positive control (MNNG), Amorphophallus konjac (A.K.), complex (MNNG+A.K.), and blank control (C) group. In MNNG group, MNNG (250 μg) was injected intravenously once five days for seven times in each mouse, the total dosage of MNNG being 1.75 mk. In A.K. group, according to w/w, 8% A.K. was well mixed into 92% common diet for long-term breeding. In complex group, MNNG was given as that in MNNG group and the mice were reared as those in A.K. group. The mice in MNNG group and in C group were all reared by common diet. The results showed different degrees of anticarcinogenic and preventive effect of refined A.K. on MNNG-induced lung cancers in LACA mice. A.K. not only exerted effect on the number of induced cancer and precancer, causing a drop of the cancerous rate from 70.87% to 19.38% and the mean number of cancer and precancer in each animal, but also postponed the incubation period. The proportional distribution of the kinds of tumor denoted a decrease in malignancy (adenoma with malignant change) , absence of adenocarcinoma, relative Increase in benign adenoma, and prolonged survival time of animals. The results of experiments in 3 batches also exhibited good duplication.展开更多
Herein we describe the discovery and functional characterization of a steroidal glycosyltransferase(SGT) from Ornithogalum saundersiae and a steroidal glycoside acyltransferase(SGA) from Escherichia coli and their app...Herein we describe the discovery and functional characterization of a steroidal glycosyltransferase(SGT) from Ornithogalum saundersiae and a steroidal glycoside acyltransferase(SGA) from Escherichia coli and their application in the biosynthesis of acylated steroidal glycosides(ASGs). Initially,an SGT gene, designated as OsSGT1, was isolated from O. saundersiae. OsSGT1-containing cell free extract was then used as the biocatalyst to react with 49 structurally diverse drug-like compounds. The recombinant OsSGT1 was shown to be active against both 3β-and 17β-hydroxyl steroids. Unexpectedly,in an effort to identify OsSGT1, we found the bacteria lacA gene in lac operon actually encoded an SGA,specifically catalyzing the acetylations of sugar moieties of steroid 17β-glucosides. Finally, a novel enzymatic two-step synthesis of two ASGs, acetylated testosterone-17-O-β-glucosides(AT-17β-Gs) and acetylated estradiol-17-O-β-glucosides(AE-17β-Gs), from the abundantly available free steroids using OsSGT1 and EcSGA1 as the biocatalysts was developed. The two-step process is characterized by EcSGA1-catalyzed regioselective acylations of all hydroxyl groups on the sugar unit of unprotected steroidal glycosides(SGs) in the late stage, thereby significantly streamlining the synthetic route towards ASGs and thus forming four monoacylates. The improved cytotoxic activities of 30-acetylated testosterone17-O-β-glucoside towards seven human tumor cell lines were thus observable.展开更多
文摘Five hundreds and fifty LACA mice were used in 3 batches for studying the anticarcinogenic effect of Konjaku powder on MNNG-induced lung cancers. These mice (within each batch) were randomly allocated to four groups, namely, positive control (MNNG), Amorphophallus konjac (A.K.), complex (MNNG+A.K.), and blank control (C) group. In MNNG group, MNNG (250 μg) was injected intravenously once five days for seven times in each mouse, the total dosage of MNNG being 1.75 mk. In A.K. group, according to w/w, 8% A.K. was well mixed into 92% common diet for long-term breeding. In complex group, MNNG was given as that in MNNG group and the mice were reared as those in A.K. group. The mice in MNNG group and in C group were all reared by common diet. The results showed different degrees of anticarcinogenic and preventive effect of refined A.K. on MNNG-induced lung cancers in LACA mice. A.K. not only exerted effect on the number of induced cancer and precancer, causing a drop of the cancerous rate from 70.87% to 19.38% and the mean number of cancer and precancer in each animal, but also postponed the incubation period. The proportional distribution of the kinds of tumor denoted a decrease in malignancy (adenoma with malignant change) , absence of adenocarcinoma, relative Increase in benign adenoma, and prolonged survival time of animals. The results of experiments in 3 batches also exhibited good duplication.
基金supported by the CAMS Innovation Fund for Medical Sciences (CIFMS, No. 2016-I2M-3–012)Beijing Natural Science Foundation (No. 7172143)
文摘Herein we describe the discovery and functional characterization of a steroidal glycosyltransferase(SGT) from Ornithogalum saundersiae and a steroidal glycoside acyltransferase(SGA) from Escherichia coli and their application in the biosynthesis of acylated steroidal glycosides(ASGs). Initially,an SGT gene, designated as OsSGT1, was isolated from O. saundersiae. OsSGT1-containing cell free extract was then used as the biocatalyst to react with 49 structurally diverse drug-like compounds. The recombinant OsSGT1 was shown to be active against both 3β-and 17β-hydroxyl steroids. Unexpectedly,in an effort to identify OsSGT1, we found the bacteria lacA gene in lac operon actually encoded an SGA,specifically catalyzing the acetylations of sugar moieties of steroid 17β-glucosides. Finally, a novel enzymatic two-step synthesis of two ASGs, acetylated testosterone-17-O-β-glucosides(AT-17β-Gs) and acetylated estradiol-17-O-β-glucosides(AE-17β-Gs), from the abundantly available free steroids using OsSGT1 and EcSGA1 as the biocatalysts was developed. The two-step process is characterized by EcSGA1-catalyzed regioselective acylations of all hydroxyl groups on the sugar unit of unprotected steroidal glycosides(SGs) in the late stage, thereby significantly streamlining the synthetic route towards ASGs and thus forming four monoacylates. The improved cytotoxic activities of 30-acetylated testosterone17-O-β-glucoside towards seven human tumor cell lines were thus observable.
