The Active Compound Thymoquinone Alters Chondrogenic Differentiation of Human Mesenchymal Stem Cells via Modulation of Intracellular Signaling.

Objective: The regenerative potential of mesenchymal stem cell (MSC)-like cells in the cartilage is relatively low because of the lack of innervation and vascularization. The increase in proinflammatory cytokines in cartilage damage can increase the expression of apoptotic and proinflammatory genes and the matrix degradation enzymes via nuclear factor-κB (NF-κB). Previous evidence suggested that thymoquinone (TQ) suppresses tumor necrosis factor-α-mediated NF-κB activation in different cancer cell lines.

Long Term Exposure to Myrtucommulone-A Changes CD105 Expression and Differentiation Potential of Mesenchymal Stem Cells.

Mesenchymal stem cells (MSCs) represent a heterogeneous group of multipotent stem cells that could be found in various somatic tissues. MSCs are defined by molecular and functional features including spindle-shape morphology, adherence to plastic surfaces, expression of specific surface markers and differentiation potential to chondrocytes, adipocytes and osteocytes. The surface markers were proposed to affect the differentiation potential of MSCs by a limited number of studies.

Current status in cancer cell reprogramming and its clinical implications.

Purpose: The technology of reprogramming a terminally differentiated cell to an embryonic-like state uncovered the possibility of reprogramming a malignant cell back to a more manageable stem cell-like state. Since the current cancer models suffer from reflecting heterogeneous tumour structure and limited to express the late-stage markers, the induced pluripotent stem cell (iPSC) technology could provide an alternative model to recapitulate the early stages of cancer. Generation of iPSCs from cancer cells could offer a tool for understanding the mechanisms of tumour initiation-progression in vitro, a platform for studying tumour heterogeneity and origin of cancer stem cells and a source for cancer type-specific drug discovery studies.

Integrin-Associated Focal Adhesion Kinase Protects Human Embryonic Stem Cells from Apoptosis, Detachment, and Differentiation.

Human embryonic stem cells (hESCs) can be maintained in a fully defined niche on extracellular matrix substrates, to which they attach through integrin receptors. However, the underlying integrin signaling mechanisms, and their contribution to hESC behavior, are largely unknown. Here, we show that focal adhesion kinase (FAK) transduces integrin activation and supports hESC survival, substrate adhesion, and maintenance of the undifferentiated state.

Reprogramming bladder cancer cells for studying cancer initiation and progression.

The induced pluripotent stem cell (iPSC) technology is the forced expression of specific transcription factors in somatic cells resulting in transformation into self-renewing, pluripotent cells which possess the ability to differentiate into any type of cells in the human body. While malignant cells could also be reprogrammed into iPSC-like cells with lower efficiency due to the genetic and epigenetic barriers in cancer cells, only a limited number of cancer cell types could be successfully reprogrammed until today. In the present study, we aimed at reprogramming two bladder cancer cell lines HTB-9 and T24 using a non-integrating Sendai virus (SeV) system.

Effects of Epirubicin and Cisplatin Against 4T1 Breast Cancer Cells are Enhanced by Myrtucommulone-A.

Background: The number of cancer cases around the world has increased according to the World Health Organization (WHO) reports, nearly 14 million new cases and 8.2 million cancer associated mortalities have been reported in 2012. Chemotherapeutic resistance is a major problematic issue in the management of patients with breast tumor.

Novel anti-cancer agent myrtucommulone-A and thymoquinone abrogate epithelial-mesenchymal transition in cancer cells mainly through the inhibition of PI3K/AKT signalling axis.

Epithelial-mesenchymal transition (EMT) plays a prominent role in cancer progression and metastasis. Inhibition of EMT-associated regulators may hold a huge promise for cancer therapy. Although TGF-β signalling has a pivotal role in the induction of EMT, alterations during the EMT process are usually initiated and controlled by the cross-talk of multiple signalling pathways, and in most cases this is context-dependent.

Inhibition of epithelial-mesenchymal transition in bladder cancer cells via modulation of mTOR signalling.

Mounting evidence suggests that signalling cross-talk plays a significant role in the regulation of epithelial-mesenchymal transition (EMT) in cancer cells. However, the complex network regulating the EMT in different cancer types has not been fully described yet which affects the development of novel therapeutic strategies. In the present study, we investigated the signalling pathways involved in EMT of bladder cancer cells and demonstrated the effects of two novel agents in the regulation of EMT.

Evaluation of two different adjuvants with immunogenic uroplakin 3A-derived peptide for their ability to evoke an immune response in mice.

Rationale: Organ- or tissue-specific antigens produced by normal tissue or by cancer cells could be used in cancer immunotherapy, to target the tumor. In our previous study, we induced T-cell-mediated, bladder-specific autoimmunity by targeting the bladder-specific protein Uroplakin 3A (UPK3A). UPK3A is a well-chosen target for developing an autoimmune response against bladder cancer since the antigen is also expressed in bladder tumors.

The combination of thymoquinone and paclitaxel shows anti-tumor activity through the interplay with apoptosis network in triple-negative breast cancer.

Thymoquinone (TQ) is the active ingredient of Nigella sativa which has a therapeutic potential in cancer therapy and prevention. In this study, TQ has been shown to induce specific cytotoxicity and apoptosis and to inhibit wound healing in triple-negative breast cancer cell line. TQ also inhibited cancer growth in a mouse tumor model.

Priming hMSCs with a putative anti-cancer compound, myrtucommulone-a: a way to harness hMSC cytokine expression via modulating PI3K/Akt pathway?

Tumour microenvironment is a key factor for cancer growth and metastasis. Tumour surrounding tissue is known to include high number of mesenchymal stem cells which have been thought to have a role in regulating cancer cell behaviour via paracrine signalling. Therefore, modulating human mesenchymal stem cell (hMSC) secretome is highly significant for controlling and treating disease.

Myrtucommulone-A treatment decreases pluripotency- and multipotency-associated marker expression in bladder cancer cell line HTB-9.

Cancer and stem cells exhibit similar features, including self-renewal, differentiation and immortality. The expression of stem-cell-related genes in cancer cells is demonstrated to be potentially correlated with cancer cell behaviour, affecting both drug response and tumor recurrence. There is an emerging body of evidence that subpopulations of tumors carry a distinct molecular sign and are selectively resistant to chemotherapy.

Myrtucommulone-A Induces both Extrinsic and Intrinsic Apoptotic Pathways in Cancer Cells.

Myrtucommulone-A is the active compound derived from Myrtus communis. The molecular targets of myrtucommulone-A is widely unknown, which impedes its potential therapeutic use. In this study, we demonstrated the cytotoxicity of MC-A and its potential to induce apoptosis in cancer cells.

Comparative proteomic analysis of supportive and unsupportive extracellular matrix substrates for human embryonic stem cell maintenance.

Human embryonic stem cells (hESCs) are pluripotent cells that have indefinite replicative potential and the ability to differentiate into derivatives of all three germ layers. hESCs are conventionally grown on mitotically inactivated mouse embryonic fibroblasts (MEFs) or feeder cells of human origin. In addition, feeder-free culture systems can be used to support hESCs, in which the adhesive substrate plays a key role in the regulation of stem cell self-renewal or differentiation.

Human feeder cell line for derivation and culture of hESc/hiPSc.

We have generated a human feeder cell line from early second trimester Placental Stromal Fibroblasts (ihPSF) stably over-expressing the polycomb protein BMI-1. These feeder cells retain the ability to maintain human Embryonic Stem cells (hESc) over long-term culture whereas hTERT or BMI-1/hTERT immortalised feeder cell lines do not. ihPSFs were able to support the derivation of a new hESc line in near xenofree (free of non-human animal components) conditions and support continued culture of newly derived hESc and human induced Pluripotent Stem (hiPS) cell lines in complete xenofree conditions necessary for clinical use.