Bioactive Potential of Several Actinobacteria Isolated from Microbiologically Barely Explored Desert Habitat, Saudi Arabia

Abstract

Biomolecules from natural sources, including microbes, have been the basis of treatment of human diseases since the ancient times. Therefore, this study aimed to investigate the potential bioactivity of several actinobacteria isolates form Al-Jouf Desert, Saudi Arabia. Twenty-one actinobacterial isolates were tested for their antioxidant (flavonoids, phenolics, tocopherols and carotenoids) content, and biological activities, namely FRAP, DPPH, ABTS, SOS and XO inhibition, anti-hemolytic and anti-lipid peroxidation as well as their antibacterial and antiprotozoal activities. Accordingly, five isolates (i.e., Act 2, 12, 15, 19 and 21) were selected and their 90% ethanolic extracts were used. The phylogenetic analysis of the 16S rRNA sequences indicated that the most active isolates belong to genus Streptomyces. The genus Streptomyces has been documented as a prolific producer of biologically active secondary metabolites against different cancer types. Thus, the anti-blood cancer activity and the possible molecular mechanisms by which several Streptomyces species extracts inhibited the growth of different leukemia cells, i.e., HL-60, K562 and THP-1, were investigated. In general, the five active isolates showed cytotoxic activity against the tested cell lines in a dose dependent manner. Among the potent isolates, isolate Act 12 significantly decreased the cell viability and showed maximum cytotoxic activities against both HL-60 and K562 cells, while isolate Act 15 exhibited maximum cytotoxic activity against THP-1 cells. Moreover, Act 2 and Act 12 reduced cyclooxygenase (COX-2) and lipoxygenase (LOX) activity, which is involved in the proliferation and differentiation of cancer cells and may represent a possible molecular mechanism underlying leukemia growth inhibition. The bioactive antioxidant extracts of the selected Streptomyces species inhibited leukemia cell growth by reducing the COX-2 and LOX activity. Overall, our study not only introduced a promising natural alternative source for anticancer agents, but it also sheds light on the mechanism underlying the anticancer activity of isolated actinomycetes.

Keywords: actinomycetes; anti-inflammatory; antioxidant; leukemia.

Figure 1

Map of Saudi Arabia showing the three soil sampling sites (Dumat Al-Jandal; Qasr Kaff and Ain Hawas Regions) of the Al-Jouf Region area.

Figure 2

Hierarchical clustering (Pearson correlation) was generated to study bioactivity of several bacterial isolates. The measured parameters are represented by antioxidant metabolites and enzymes, overall antioxidant capacity (FRAP, DPPH, ABTS, SOS and XO inhibition), anti-hemolytic and anti-lipid peroxidation as well as their antibacterial and antiprotozoal activity. Data are represented by the means of at least three replicates.

Figure 3

The evolutionary analysis of the five most biologically active actinobacterial isolates as analyzed by phylogenetic tree constructed by the maximum likelihood method using MEGAX software for the 16S rRNA sequences of Streptomyces spp. Act 2, Act 12, Act 15, Act 19 and Act 21. The numbers at nodes represent the percentage values given by 1000 bootstrap samples analysis.

Figure 4

The activity of 90% ethanol extracts (0, 10, 25, 50, 100, 200, 300, 400, 800 µg/mL) of five most biologically active Streptomyces isolates (Act 2, Act 12, Act 15, Act 19 and Act 21) against leukemia cell viability (HL-60, K562 and THP-1). Data are represented by the means of at least 3 replicates and error bars represent standard deviations.

Figure 5

The effect of the 90% ethanol extract of the five most biologically active Streptomyces isolates (Act 2, Act 12, Act 15, Act 19 and Act 21) on cyclooxygenase (COX-2) and lipoxygenase (LOX) activity. Data are represented by the means of at least 3 replicates and error bars represent standard deviations. Different letters above the bars indicate significant differences (p < 0.05, Tuckey test).