Mesenchymal stem cells (MSCs) are of special interest due their potential clinical use in cell-based therapy. Therapies engaging MSCs are showing increasing promise in the cancer treatment and anticancer drug screening applications. A multitude of growth factors and cytokines secreted from these cells are known to give such multifunctional properties, but details of their role are yet to be absolutely demonstrated. In this study, we have evaluated the influence of BMSCs on K562 cell line as chronic myeloid leukemia (CML) cells, with the use of a cytokine antibody array recognizing 34 cytokines. For this purpose, BMSCs were isolated and co-cultured with K562 cells; thereafter, cultured K562 alone and co-cultured K562 with BMSCs (10:1) were collected at day 7 and subjected to cell cycle distribution assay as well as annexin/PI analysis and Ki/caspase-3 assay for apoptosis assessment. In the following, the gene and protein expression levels of BAX and BCL-2 as pro- and anti-apoptotic agents were investigated. Furthermore, after 7 days’ treatment, culture medium was collected from both control and experimental groups for cytokine antibody array. It was found that BMSCs resulted in a robust increase in the number of cells at G 0 /G 1 phase and arrest the G 0 /G 1 phase as well as significantly inducing late apoptosis in K562 cells. The significant presence of TIMP-1 (tissue inhibitor of metalloproteinases-1), and moderate elevated signals for CINC-1 (cytokine-induced neutrophil chemoattractant-1) were obvious in the co-cultured conditioned media, but no significant increase was found in 32 other cytokines. It is concluded that co-culture of BMSCs with K562 cells could secrete a substantial amount of TIMP-1 and CINC-1. These cytokines could be involved in the inhibition of the K562 cell proliferation via BAX and caspase-3 cascade pathways.

Natural killer (NK) cells have significant capability in tumor immune-surveillance. The ability of lyse transformed cells immediately in an antigen-independent manner make them an attractive candidate for cancer cell therapy. Despite employment of NK cells in cancer immunotherapy, clinical trials are faced with serious limitations such as trouble with the penetration of NK cells in tumor sites, limited in vivo persistence, and tumor microenvironment interference. Taken together, the NK-cell cancer therapy is still infant scenario that has a long way to be translated in clinic. Current article first reviews characteristic features of NK lymphocytes. Then, it discusses about important disruptive barriers and motivator in the developmental stages of NK cells like as tumor microenvironment. Finally, some revolutionary approaches are highlighted utilizing of NK cells in cancer therapy.

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Purpose: The effect of mesenchymal stem cells (MSCs) on the immortality features of malignant cells, such as hematologic cancerous cells, are controversial, and the associated mechanisms are yet to be well understood. The aim of the present study was to investigate the in vitro effect of bone marrow-derived MSCs (BMSCs) on the chronic myeloid leukemia cell line K562 through telomere length measurements, telomerase activity assessments, and hTERT gene expression. The possible signaling pathways involved in this process, including Wnt-5a/β-catenin and P53, were also evaluated. Methods: Two cell populations (BMSCs and K562 cell line) were co-cultured on transwell plates for 7 days. Next, K562 cells were collected and subjected to quantitative real-time PCR, PCR-ELISA TRAP assay, and the ELISA sandwich technique for telomere length, hTERT gene expression, telomerase activity assay, and cytokine measurement, respectively. Also, the involvement of the mentioned signaling pathways in this process was reported by real-time PCR and Western blotting through gene and protein expression, respectively. Results: The results showed that BMSCs caused significant decreases in telomere length, telomerase activity, and the mRNA level of hTERT as a regulator of telomerase activity. The significant presence of interleukin (IL)-6, IL-8, and transforming growth factor beta (TGF-β) was obvious in the co-cultured media. Also, BMSCs significantly decreased and increased the gene and protein expression of β-catenin and P53, respectively. Conclusion: It was concluded that the mentioned effects of IL-6, IL-8, and TGF-β cytokines secreted from MSCs on K562 cells as therapeutic agents were applied by Wnt-5a/β-catenin and P53 pathways

Purpose: The PI3K/Akt signaling pathway regulates cell growth, proliferation and viability in hematopoietic cells. This pathway always dysregulates in acute lymphoblastic leukemia (ALL). PTEN and P53 are tumor suppressor genes correlated with PI3K/Akt signaling pathway, and both have a tight link in regulation of cell proliferation and cell death. In this study, we investigated the effects of dual targeting of PI3K/Akt pathway by combined inhibition with nvp-BKM-120 (PI3K inhibitor) and MK-2206 (Akt inhibitor) in relation with PTEN and P53 on apoptosis and proliferation of leukemia cells. Methods: Both T and B ALL cell lines were treated with both inhibitors alone or in combination with each other, and induction of apoptosis and inhibition of proliferation were evaluated by flow cytometry. Expression levels of PTEN as well as p53 mRNA and protein were measured by real-time qRT-PCR and western blot, respectively. Results: We indicated that both inhibitors (BKM-120 and MK-2206) decreased cell viability and increased cytotoxicity in leukemia cells. Reduction in Akt phosphorylation increased PTEN and p53 mRNA and p53 protein level (in PTEN positive versus PTEN negative cell lines). Additionally, both inhibitors, particularly in combination with each other, increased apoptosis (evaluated with Annexin V and caspase 3) and reduced proliferation (Ki67 expression) in leukemia cells. However, administration of IL7 downregulated PTEN and P53 mRNA expression and rescued cancer cells following inhibition of BKM-120 and MK-2206. Conclusion: This investigation suggested that inhibition of Akt and PI3K could be helpful in leukemia treatment.