Culture filtrate ether extracted metabolites from Streptomyces levis ABRIINW111 increased apoptosis and reduced proliferation in acute lymphoblastic leukemia.

Despite the advances in the discovery of various types of anticancer drugs for curing acute lymphoblastic leukemia (ALL), their toxicity and unfavorable side effects remained as big limitations for therapeutical applications. In this regard, natural products such as Streptomyces -derived agents have shown potential applications as anticancer drugs. The present study deals with evaluating the anti-carcinogenic activity of the ether extracted metabolites derived from Streptomyces on nalm-6 and molt-4 ALL cell lines. MTT assay was performed to evaluate the cytotoxicity effect of Streptomyces sp on nalm-6 and molt-4 cell lines. Apoptosis and proliferation were evaluated by Flow cytometry. Quantitative real-time RT-PCR (qRT-PCR) and western blot were performed to investigate the effect of these metabolites on the mRNA and protein expression levels of P53, Bax, and Bcl2. In both cell lines, extracted metabolites significantly inhibited cell growth and increased apoptosis. Although P53, Bax mRNA and protein expressions were increased, Bcl-2 expression decreased in treated cells compared with control. In addition, the G0/G1 arrest of Nalm-6 cells was induced. These findings of this work show that the ether-extracted metabolites from Streptomyces levis ABRIINW111 can be used as an anti-carcinogenic for acute lymphoblastic leukemia cells.

Streptomyces Levis ABRIINW111 Inhibits SW480 Cells Growth by Apoptosis Induction.

Purpose: Streptomyces sp., a dominant genus in Actinomycetes, is the source of a wide variety of secondary metabolites. Microbial metabolites can be utilized as novel anticancer agents; with fewer side effects. The present article illustrated the anti-carcinogenic effect of the ether extracted organic metabolites derived from Streptomyces bacteria on SW480 colon cancer cell line. Methods: MTT assay was performed in order to investigate the cytotoxicity effect of metabolites on SW480 cells. Apoptosis and cell cycle arrests were measured by flowcytometry. Morphological changes were indicated by Propidium iodide staining andP53 gene expression was evaluated by real-time PCR. Results: Streptomyces Levis ABRIINW111 inhibited cell growth, increased Caspases 3 and reduced Ki67 expression in a concentration/time-dependent manner in SW40 cells. Metabolites increased subG1 phase (apoptosis) and also cell cycle arrest in G1, G---2/M and S phase. P53 gene expression followed Sw480 cells treatment significantly. Conclusion: Streptomyces sp. metabolites have anti-carcinogenic effect on colon cancer cells. Streptomyces Levis ABRIINW111 metabolites are a candidate for Colon cancer treatment.

The impact of different extracellular matrices on melatonin effect in proliferation and stemness properties of ovarian cancer cells.

AIM: Endogenous melatonin has numerous physiological roles on modulating the function of different organs. Recent studies revealed oncostatic and protective effects of this molecule on tumor development. In this study, we examined the impact of melatonin and key underlying mechanisms on stemness, morphology, invasiveness and viability of SKOV3 ovarian cancer cells in different types of extracellular matrix. METHODS: Cell viability was evaluated by MTT Assay. Colony-forming assay was performed by seeding 4×103 cells on different matrices in six well-plate. The percentage of cancer stem like cells was determined by flow cytometric assay after applying antibodies against stemness markers, CD133 and CD44. Different types of extracellular matrix including fibronectin, gelatin, collagen and matrigel were applied to incubate the cells in the presence of melatonin. Downstream gene expressions including VEGF and E-cadherin were determined by Real-time PCR. RESULTS: Melatonin (0.1mM) decreased the percentage of viable cells up to 61.79±8.2% (p<0.05). Colony formation assay revealed the significant impact of melatonin in inhibition of colony formation in these cells. The maximum effect was shown in the cells incubated with melatonin on gelatin (p<0.05). Identification of stemness markers showed that applying matrigel caused significant increase in the percentage of cancer stem like cells compared to other types of extracellular matrix (p<0.05). However melatonin slightly diminished the number of stem cell like cells in all incubated matrices. Our results from gene expression assays revealed that melatonin induced a marked increase in E-cadherin along with decrease in VEGF expression levels (p<0.05). CONCLUSION: Our results suggest that interaction between ovarian cancer cells and neighboring matrices determines the subsequent anti invasive activities of melatonin.