Curcumin inhibits cellular condensation and alters microfilament organization during chondrogenic differentiation of limb bud mesenchymal cells

Sureshbabul

Evidence-Based Complementary and Alternative Medicine

et al. 2013

Colorectal cancer (CRC) is a serious public health problem that results due to changes of diet and various environmental stress factors in the world. Curcumin is a traditional medicine used for treatment of a wide variety of tumors. However, antimetastasis mechanism of curcumin on CRC has not yet been completely investigated. Here, we explored the underlying molecular mechanisms of curcumin on metastasis of CRC cells in vitro and in vivo. Curcumin significantly inhibits cell migration, invasion, and colony formation in vitro and reduces tumor growth and liver metastasis in vivo. We found that curcumin suppresses Sp-1 transcriptional activity and Sp-1 regulated genes including ADEM10, calmodulin, EPHB2, HDAC4, and SEPP1 in CRC cells. Curcumin inhibits focal adhesion kinase (FAK) phosphorylation and enhances the expressions of several extracellular matrix components which play a critical role in invasion and metastasis. Curcumin reduces CD24 expression in a dose-dependent manner in CRC cells. Moreover, E-cadherin expression is upregulated by curcumin and serves as an inhibitor of EMT. These results suggest that curcumin executes its antimetastasis function through downregulation of Sp-1, FAK, and CD24 and by promoting E-cadherin expression in CRC cells.

Section: Discussionsupporting

confidence: 90%

Curcumin Suppresses Metastasis via Sp-1, FAK Inhibition, and E-Cadherin Upregulation in Colorectal Cancer

Sureshbabul

Evidence-Based Complementary and Alternative Medicine

et al. 2013

Tissue Engineering Part A

“…23 The early and extensive cell-cell interaction in the PLCL/chitosan was followed by subsequent reorganization of actin cytoskeletal to the cortical with a concomitant rounding of cells forming cell aggregation, an event reported to associate with the activation of stem cells chondrogenic differentiation. [24][25][26] Taken together, our data indicate that provision of the scaffold surface with chitosan coating greatly enhanced MSC distribution in the scaffold. The strikingly different morphology acquired by the MSCs on attachment to the two scaffolds might have a direct effect on subsequent differentiation.…”

Section: Discussionsupporting

confidence: 55%

Improved Mesenchymal Stem Cells Attachment andIn VitroCartilage Tissue Formation on Chitosan-Modified Poly(l-Lactide-co-Epsilon-Caprolactone) Scaffold

Yang

et al. 2012

Considering the load-bearing physiological requirement of articular cartilage, scaffold for cartilage tissue engineering should exhibit appropriate mechanical responses as natural cartilage undergoing temporary deformation on loading with little structural collapse, and recovering to the original geometry on unloading. A porous elastomeric poly l-lactide-co-ɛ-caprolactone (PLCL) was generated and crosslinked at the surface to chitosan to improve its wettability. Human bone marrow derived mesenchymal stem cells (MSC) attachment, morphological change, proliferation and in vitro cartilage tissue formation on the chitosan-modified PLCL scaffold were compared with the unmodified PLCL scaffold. Chitosan surface promoted more consistent and even distribution of the seeded MSC within the scaffold. MSC rapidly adopted a distinct spread-up morphology on attachment on the chitosan-modified PLCL scaffold with the formation of F-actin stress fiber which proceeded to cell aggregation; an event much delayed in the unmodified PLCL. Enhanced cartilage formation on the chitosan-modified PLCL was shown by real-time PCR analysis, histological and immunochemistry staining and biochemical assays of the cartilage extracellular matrix components. The Young's modulus of the derived cartilage tissues on the chitosan-modified PLCL scaffold was significantly increased and doubled that of the unmodified PLCL. Our results show that chitosan modification of the PLCL scaffold improved the cell compatibility of the PLCL scaffold without significant alteration of the physical elastomeric properties of PLCL and resulted in the formation of cartilage tissue of better quality.

“…We chose this concentration based on previous studies in our laboratory demonstrating that canine MSCs do not tolerate curcumin concentrations higher than 5 μM. A recent study by Kim and co-workers demonstrated that chick MSCs treated with 20 μM curcumin become apoptotic and do not undergo chondrogenesis [ 39 ]. This clearly demonstrates that MSCs can only tolerate lower concentrations of curcumin in contrast to chondrocytes [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

Curcumin mediated suppression of nuclear factor-κB promotes chondrogenic differentiation of mesenchymal stem cells in a high-density co-culture microenvironment

et al. 2010

IntroductionOsteoarthritis (OA) and rheumatoid arthritis (RA) are characterised by joint inflammation and cartilage degradation. Although mesenchymal stem cell (MSC)-like progenitors are resident in the superficial zone of articular cartilage, damaged tissue does not possess the capacity for regeneration. The high levels of pro-inflammatory cytokines present in OA/RA joints may impede the chondrogenic differentiation of these progenitors. Interleukin (IL)-1β activates the transcription factor nuclear factor-κB (NF-κB), which in turn activates proteins involved in matrix degradation, inflammation and apoptosis. Curcumin is a phytochemical capable of inhibiting IL-1β-induced activation of NF-κB and expression of apoptotic and pro-inflammatory genes in chondrocytes. Therefore, the aim of the present study was to evaluate the influence of curcumin on IL-1β-induced NF-κB signalling pathway in MSCs during chondrogenic differentiation.MethodsMSCs were either cultured in a ratio of 1:1 with primary chondrocytes in high-density culture or cultured alone in monolayer with/without curcumin and/or IL-1β.ResultsWe demonstrate that although curcumin alone does not have chondrogenic effects on MSCs, it inhibits IL-1β-induced activation of NF-κB, activation of caspase-3 and cyclooxygenase-2 in MSCs time and concentration dependently, as it does in chondrocytes. In IL-1β stimulated co-cultures, four-hour pre-treatment with curcumin significantly enhanced the production of collagen type II, cartilage specific proteoglycans (CSPGs), β1-integrin, as well as activating MAPKinase signaling and suppressing caspase-3 and cyclooxygenase-2.ConclusionsCurcumin treatment may help establish a microenvironment in which the effects of pro-inflammatory cytokines are antagonized, thus facilitating chondrogenesis of MSC-like progenitor cells in vivo. This strategy may support the regeneration of articular cartilage.