Antitumor activity of 4-Arylcoumarins from endophytic Streptomyces aureofaciens CMUAc130

Abstract

In a search for antitumor agents, we carried out a screening of 4-arylcoumarins isolated from endophytic Streptomyces aureofaciens CMUAc130, by examining their possible inhibitory effect on the growth of s.c. transplanted Lewis lung carcinoma (LLC) in BDF-1 mice by intraperitoneal (i.p.) administration. The 4-arylcoumarins showed antitumor activity with T/C values of 80.8 and 50.0% at doses of 1 and 10 mg/kg of 5,7-dimethoxy-4-p-methoxylphenylcoumarin treatment, respectively and 81.5 and 44.9% at doses of 1 and 10 mg/kg of 5,7-dimethoxy-4-phenylcoumarin treatment, respectively, compared to adriamycin, which was used a positive control, with T/C value of 55.9% at 2 mg/kg. Furthermore, we investigated the possible effects of these compounds on expression of the bcl-2 and Bax oncoproteins in A427, a human lung cancer cell lines. The cells were cultured in vitro for 24 h in RPMI 1640 with 1.5% (v/v) ethanol, 100 microg/ml 5,7-dimethoxy-4-p-methoxylphenylcoumarin or 5,7-dimethoxy-4-phenylcoumarin. Viability was determined by an MTT assay. Total protein was extracted from cell lysates and the bcl-2 and Bax oncoproteins were identified. Western blotting showed a decrease in bcl-2 and an increase in Bax in A427 cell cultured with 5,7-dimethoxy-4-p-methoxylphenylcoumarin or 5,7-dimethoxy-4-phenylcoumarin. We conclude that 5,7-dimethoxy-4-phenylcoumarin is a more potent inhibitor of cell proliferation than 5,7-dimethoxy-4-p-methoxylphenylcoumarin and has more marked effects on oncoprotein expression.

Diversity and bioprospecting of actinomycete endophytes from the medicinal plants

“…4-Arylcoumarin analogs from Streptomyces aureofaciens CMUAc130 showed antitumour activity by their inhibitory effects on transplanted LLC in mice. The biochemical mechanisms for the inhibition of tumour proliferation was experimented with adenocarcinoma cell line (A427) for the overexpression of oncoproteins which suggested that 5,7-dimethoxy-4-phenylcoumarin delayed the intracellular signal leading to tumour proliferation (Taechowisan et al 2007). Brartemicin an antibiotic and a novel inhibitor of metastasis produced by Micromonospora sp., was isolated from the Brazilian medicinal plant, Artemisia vulgaris (Igarashi et al 2009).…”

Chemical and Functional Diversity of Natural Products from Plant Associated Endophytic Fungi

“…A new anti-inflammatory compound, 5, 7-dimethoxy-4-p-methoxylphenylcoumarin (118), and 5, 7dimethoxy-4-phenylcoumarin (119) were isolated from endophytic Streptomyces aureofaciens CMUAc130 [103,104].…”

Rational Design, Synthesis and Evaluation of Coumarin Derivatives as Protein‐protein Interaction Inhibitors

“…It is well‐known that coumarins are a versatile class of heterocycles displaying a wide range of therapeutic activities. Particularly, coumarin derivatives have been shown to be pharmacologically useful as anti‐coagulants, anti‐oxidants, antitumorals, free radical scavengers and also anti‐HIV agents …”