Evaluation of the anticarcinogenic potential of the endophyte, Streptomyces sp. LRE541 isolated from Lilium davidii var. unicolor (Hoog) Cotton.

BACKGROUND: Endophytic actinomycetes, as emerging sources of bioactive metabolites, have been paid great attention over the years. Recent reports demonstrated that endophytic streptomycetes could yield compounds with potent anticancer properties that may be developed as chemotherapeutic drugs. RESULTS: Here, a total of 15 actinomycete-like isolates were obtained from the root tissues of Lilium davidii var. unicolor (Hoog) Cotton based on their morphological appearance, mycelia coloration and diffusible pigments. The preliminary screening of antagonistic capabilities of the 15 isolates showed that isolate LRE541 displayed antimicrobial activities against all of the seven tested pathogenic microorganisms. Further in vitro cytotoxicity test of the LRE541 extract revealed that this isolate possesses potent anticancer activities with IC50 values of 0.021, 0.2904, 1.484, 4.861, 6.986, 8.106, 10.87, 12.98, and 16.94 µg/mL against cancer cell lines RKO, 7901, HepG2, CAL-27, MCF-7, K562, Hela, SW1990, and A549, respectively. LRE541 was characterized and identified as belonging to the genus Streptomyces based on the 16S rRNA gene sequence analysis. It produced extensively branched red substrate and vivid pink aerial hyphae that changed into amaranth, with elliptic spores sessile to the aerial mycelia. To further explore the mechanism underlying the decrease of cancer cell viability following the LRE541 extract treatment, cell apoptosis and cell cycle arrest assays were conducted in two cancer cell lines, RKO and 7901. The result demonstrated that LRE541 extract inhibited cell proliferation of RKO and 7901 by causing cell cycle arrest both at the S phase and inducing apoptosis in a dose-dependent manner. The chemical profile of LRE541 extract performed by the UHPLC-MS/MS analysis revealed the presence of thirty-nine antitumor compounds in the extract. Further chemical investigation of the LRE541 extract led to the discovery of one prenylated indole diketopiperazine (DKP) alkaloid, elucidated as neoechinulin A, a known antitumor agent firstly detected in Streptomyces; two anthraquinones 4-deoxy-ε-pyrromycinone (1) and epsilon-pyrromycinone (2) both displaying anticancer activities against RKO, SW1990, A549, and HepG2 with IC50 values of 14.96 ± 2.6 - 20.42 ± 4.24 µg/mL for (1); 12.9 ± 2.13, 19.3 ± 4.32, 16.8 ± 0.75, and 18.6 ± 3.03 µg/mL for (2), respectively. CONCLUSION: Our work evaluated the anticarcinogenic potential of the endophyte, Streptomyces sp. LRE541 and obtained one prenylated indole diketopiperazine alkaloid and two anthraquinones. Neoechinulin A, as a known antitumor agent, was identified for the first time in Streptomyces. Though previously found in Streptomyces, epsilon-pyrromycinone and 4-deoxy-ε-pyrromycinone were firstly shown to possess anticancer activities.

Effects of environmental factors on anthocyanin accumulation in the fruits of Lycium ruthenicum Murray across different desert grasslands.

Anthocyanins can help plants adapt and resist adverse environments and have important nutritional and medicinal effects on human beings. However, how environmental factors affect the anthocyanins accumulation of plants and how to improve the anthocyanins content of plants in different soils needs further exploration. Hence, this study aimed to investigate the effects of environmental factors on the accumulation of cyanidin, petunidin, malvidin, and delphinidin in the fruits of Lycium ruthenicum in sandy desert grassland (SS), gravel desert grassland (GD), and saline-alkali desert grassland (SD) in the lower reaches of the Shiyang River Basin. The variable importance screened the key environmental factors affecting anthocyanin accumulation in projection (VIP) and multiple stepwise regressions. The structural equation model (SEM) was established to understand how the climate and soil factors affect the total anthocyanin accumulation. For establishing soil nutrient optimization schemes by partial least squares regression (PLS) and the simplex algorithm used to improve the anthocyanin content in different types of desert grassland. In SS, electrical conductivity (EC) and microbial biomass carbon (SMBC) showed highly significant and positive effects on the content of total anthocyanin, cyanidin, and petunidin. In GD, soil moisture and microbial biomass nitrogen (SNBN) significantly negatively affected total anthocyanin content. In SD, catalase (CAT), phosphatase (PHO), and total potassium (TK) had the greatest impact on total anthocyanin content. It is indicated that the targeted improvement measures are necessary to increase anthocyanin content in the fruit of Lycium ruthenicum.

Phylogenetic and Physiological Diversity of Cultivable Actinomycetes Isolated From Alpine Habitats on the Qinghai-Tibetan Plateau.

Actinomycetes in extreme alpine habitat have attracted much attention due to their unique physiological activities and functions. However, little is known about their ecological distribution and diversity. Here, we explored the phylogenetic relationship and physiological heterogeneity of cultivable actinomycetes from near-root soils of different plant communities in the Laohu Ditch (2200 - 4200 m) and Gaize County area (5018 - 5130 m) on the Qinghai-Tibetan Plateau. A total of 128 actinomycete isolates were obtained, 16S rDNA-sequenced and examined for antimicrobial activities and organic acid, H2S, diffusible pigments, various extracellular enzymes production. Seventy three isolates of the total seventy eight isolates from the Laohu Ditch, frequently isolated from 2200 to 4200 m, were closely related to Streptomyces spp. according to the 16S rDNA sequencing, while four isolates within the genus Nocardia spp. were found at 2200, 2800, and 3800 m. In addition, one potential novel isolate with 92% sequence similarity to its nearest match Micromonospora saelicesensis from the GenBank database, was obtained at 2200 m. From the Gaize County area, fifty Streptomyces isolates varied in diversity at different sites from 5018 to 5130 m. The investigation of phenotypic properties of 128 isolates showed that 94.5, 78.9, 68, 64.8, 53, 51.6, 50, 36.7, 31.2, and 22.7% of the total isolates produced catalase, lipase 2, urease, protease, H2S, lipase 3, amylase, lipase 1, diffusible pigment and organic acid, respectively. The antimicrobial assays of the total isolates revealed that 5, 28, 19, and 2 isolates from Streptomyces spp. exhibited antimicrobial activity against Escherichia coli, Staphylococcus aureus, Candida albicans, and Pseudomonas aeruginosa, respectively. This study intends to bring helpful insights in the exploitation and utilization of alpine actinomycetes for novel bioactive compounds discovery.