Phytochemical Profiles and Anticancer Effects of Calophyllum inophyllum L. Extract Relating to Reactive Oxygen Species Modulation on Patient-Derived Cells from Breast and Lung Cancers.

Reactive oxygen species (ROS) contribute to cancer growth and metastasis. Using antioxidants to modulate cellular ROS levels is a promisingstrategy for cancer prevention and treatment. Calophyllum inophyllum L., or tamanu, is a medicinal plant renowned for its anti-inflammatory, antioxidant, and anticancer properties in traditional medicine systems. However, the anticancer effects of C. inophyllum extract on cellular ROS remain unexplored. This study represents the first report on such effects and provides the potential mechanisms underlying the anticancer properties of C. inophyllum extract. The branches of C. inophyllum were extracted, and the extract was comprehensively analyzed for phytochemical constituents, antioxidant capacity, total phenolic content, and total flavonoid content. Subsequently, the extract's potential anticancer properties were evaluated using patient-derived cells from breast and lung cancer. The results revealed that the C. inophyllum extract possesses notable antioxidant activity and demonstrated no cytotoxicity within the initial 24 h of treatment. However, after 72 h, it exhibited significant antiproliferative effects. Moreover, the extract exhibited inhibitory properties against migration and invasion at concentrations below the IC50, which corresponded to the expression of related genes. Notably, these effects correlated with the reduction of intracellular ROS levels. Overall, our findings highlight the anticancer potential of C. inophyllum extract, emphasize its ability to modulate cellular ROS levels and target key molecular pathways involved in cancer progression. This study sheds light on the promising therapeutic implications of C. inophyllum extract as a novel agent for cancer treatment, which is safe for normal cells.

Intrinsic Cellular Responses of Human Wharton's Jelly Mesenchymal Stem Cells Influenced by O2-Plasma-Modified and Unmodified Surface of Alkaline-Hydrolyzed 2D and 3D PCL Scaffolds.

Polycaprolactone (PCL), a hydrophobic-degradable polyester, has been widely investigated and extensively developed, to increase the biocompatibility for tissue engineering. This research was the first trial to evaluate the intrinsic biological responses of human Wharton's Jelly Mesenchymal Stem Cells (hWJMSCs) cultured on alkaline hydrolysis and low-pressure oxygen plasma modified 2D and 3D PCL scaffolds, without adding any differentiation inducers; this has not been reported before. Four types of the substrate were newly established: 2D plasma-treated PCL (2D-TP), 2D non-plasma-treated PCL (2D-NP), 3D plasma-treated PCL (3D-TP), and 3D non-plasma-treated PCL (3D-NP). Physicochemical characterization revealed that only plasma-treated PCL scaffolds significantly increased the hydrophilicity and % oxygen/carbon ratio on the surfaces. The RMS roughness of 3D was higher than 2D conformation, whilst the plasma-treated surfaces were rougher than the non-plasma treated ones. The cytocompatibility test demonstrated that the 2D PCLs enhanced the initial cell attachment in comparison to the 3Ds, indicated by a higher expression of focal adhesion kinase. Meanwhile, the 3Ds promoted cell proliferation and migration as evidence of higher cyclin-A expression and filopodial protrusion, respectively. The 3Ds potentially protected the cell from apoptosis/necrosis but also altered the pluripotency/differentiation-related gene expression. In summary, the different configuration and surface properties of PCL scaffolds displayed the significant potential and effectiveness for facilitating stem cell growth and differentiation in vitro. The cell-substrate interactions on modified surface PCL may provide some information which could be further applied in substrate architecture for stem cell accommodation in cell delivery system for tissue repair.

Biocompatibility Assessment of PLCL-Sericin Copolymer Membranes Using Wharton's Jelly Mesenchymal Stem Cells.

Stem cells based tissue engineering requires biocompatible materials, which allow the cells to adhere, expand, and differentiate in a large scale. An ideal biomaterial for clinical application should be free from mammalian products which cause immune reactivities and pathogen infections. We invented a novel biodegradable poly(L-lactic-co-ε-caprolactone)-sericin (PLCL-SC) copolymer membrane which was fabricated by electrospinning. Membranes with concentrations of 2.5 or 5% (w/v) SC exhibited qualified texture characteristics with a noncytotoxic release profile. The hydrophilic properties of the membranes were 35-40% higher than those of a standard PLCL and commercial polystyrene (PS). The improved characteristics of the membranes were due to an addition of new functional amide groups, C=O, N-H, and C-N, onto their surfaces. Degradation of the membranes was controllable, depending on the content proportion of SC. Results of thermogram indicated the superior stability and crystallinity of the membranes. These membranes enhanced human Wharton's jelly mesenchymal stem cells (hWJMSC) proliferation by increasing cyclin A and also promoted cell adhesion by upregulating focal adhesion kinase (FAK). On the membranes, hWJMSC differentiated into a neuronal lineage with the occurrence of nestin. These data suggest that PLCL-SC electrospun membrane represents some properties which will be useful for tissue engineering and medical applications.

Effect of topology of poly(L-lactide-co-ε-caprolactone) scaffolds on the response of cultured human umbilical cord Wharton's jelly-derived mesenchymal stem cells and neuroblastoma cell lines.

In this study, for the first time, a biodegradable poly(L-lactide-co-ε-caprolactone), PLC 67:33 copolymer was developed for use as temporary scaffolds in reconstructive nerve surgery. The effect of the surface topology and pore architecture were studied on the biocompatibility for supporting the growth of human umbilical cord Wharton's jelly-derived mesenchymal stem cells (hWJ-MSCs) and human neuroblastoma cells (hNBCs) as cell models. Porous PLC membranes were prepared by electrospinning and phase immersion precipitation with particulate leaching and nonporous PLC membranes were prepared by solvent casting. From the results, the porous PLC membranes can support hWJ-MSCs and hNBCs cells better than the nonporous PLC membrane, and the interconnected pore scaffold prepared by electrospinning exhibited a more significant supporting attachment of the cells than the open pore and nonporous membranes. We can consider that these electrospun PLC membranes with 3-D interconnecting fiber networks and a high porosity warrant a potential use as nerve guides in reconstructive nerve surgery.

Improving the attachment and proliferation of umbilical cord mesenchymal stem cells on modified polystyrene by nitrogen-containing plasma.

Wharton's jelly mesenchymal stem cells (WJMSCs) are important alternative source of pluripotent cells for several therapeutic purposes. Understanding of adhesion properties of such cells is necessary to regulate the attachment, growth and proliferation on targeted culture surfaces. BCP-K1, a line of WJMSCs, and polystyrene (PS) culture dishes were used as membrane samples. A 13.56 MHz inductively coupled discharge plasma reactor with a mixture of N-containing gas and noble gas was used. This was expected to introduce the more hydrophilic groups on PS surface and enhance the cell adhesion. The plasma-treated PS dishes with the mixed gas of N(2) + He at 50 W and NH(3) + He at 100 W were reactive towards BCP-K1. Cellular adhesion and proliferation was significantly twice as efficient on the treated surfaces than on PS dishes. BCP-K1 also secreted more focal adhesion kinase to adhere and proliferate when cultured on N(2)-treated PS dishes than on the NH(3)-treated PS dishes. Stable stemness markers were detected, including CD105, CD9 and SSEA-4, expressed on BCP-K1 growing on the modified PS dish surfaces, during 7 days of culturing. The presence of -NH(2) groups on the PS dish surface were revealed by X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy. A large amount of oxygen- and nitrogen-containing functional groups, up to 9.0 %, were introduced by NH(3) plasma and N(2) plasma. The functional groups introduced on to the PS surfaces were clearly the key factors which enhanced WJMSCs attachment and stemness stability.