Assessment of resistomycin, as an anticancer compound isolated and characterized from Streptomyces aurantiacus AAA5

Abstract

A new actinomycete strain, isolated from humus soils in the Western Ghats, was found to be an efficient pigment producer. The strain, designated AAA5, was identified as a putative Streptomyces aurantiacus strain based on cultural properties, morphology, carbon source utilization, and analysis of the 16S rRNA gene. The strain produced a reddish-brown pigmented compound during the secondary metabolites phase. A yellow compound was derived from the extracted pigment and was identified as the quinone-related antibiotic resistomycin based on ultraviolet-visible spectrophotometry, fourier transform infrared spectroscopy, liquid chromatography and mass spectroscopy, and nuclear magnetic resonance analyses. The AAA5 strain was found to produce large quantities of resistomycin (52.5 mg/L). It showed potent cytotoxic activity against cell lines viz. HepG2 (hepatic carcinoma) and HeLa (cervical carcinoma) in vitro, with growth inhibition (GI(50)) of 0.006 and 0.005 μg/ml, respectively. The strain also exhibited broad antimicrobial activities against both Gram-positive and Gram-negative bacteria. Therefore, AAA5 may have great potential as an industrial resistomycin-producing strain.

Isolation of Resistomycin from a Terrestrial Actinomycete with TRAIL Resistance-overcoming Activity

“…In the present study, the bioassayguided separation of an extract of the cultured media of the actinomycete strain CKK1172 led to the isolation of resistomycin (1). The antimicrobial and cytotoxic activities of 1 were described previously [8], while we herein reported the TRAIL resistanceovercoming activity of 1 at 2 µM in AGS cells for the first time, thereby suggesting their possible use in combination with TRAIL against AGS cells.…”

“…A large-scale culture using liquid Waksman media (11.2 L) with shaking at 28 °C for 5 days was separated into a supernatant and mycelia by centrifugation. The EtOAc-soluble fraction of the supernatant of the culture was subjected to silica gel and ODS column chromatography, followed by preparative ODS HPLC to provide resistomycin (1, ESIMS m/z 377 [M+H] + ) (Figure 1), which was identified by comparisons with published spectral data [7,8]. The occurrence of resistomycin (1) was previously reported from culture broths of several kinds of actinomycetes [7][8][9][10].…”

“Function-First” Lead Discovery: Mode of Action Profiling of Natural Product Libraries Using Image-Based Screening

“…The identity of each compound was verified by (−)-FTICR MS and analysis of NMR spectra (Figure S1). All three of these compounds have reported cytotoxicity against mammalian cells (Martin et al, 2002; Gorajana et al, 2007; Vijayabharathi et al, 2011). Furthermore, resistomycin has recently been shown to bind DNA by fluorescence competition experiments and circular dichroism studies (Vijayabharathi et al, 2012), and to prevent transcription by inhibition of RNA polymerase (Arora, 1985).…”

Antibacterial and anticancer activity of marineStreptomyces parvus: optimization and application

“…In a similar study, Vijayabharathi et al [53] reported that Sterptomyces strain, isolated from humus soils in the Western Ghats, has an anticancer activity against HepG2 (hepatic carcinoma) and HeLa (cervical carcinoma) in vitro. Secondary metabolites from actinomycetes, Figure 6.…”