Natural products remain a popular alternative treatment for many ailments in various countries. This study aimed to screen for potential mammalian target of rapamycin (mTOR) inhibitors from Malaysian natural substance, using the Natural Product Discovery database, and to determine the IC50 of the selected mTOR inhibitors against UMB1949 cell line. The crystallographic structure of the molecular target (mTOR) was obtained from Protein Data Bank, with Protein Data Bank (PDB) ID: 4DRI. Everolimus, an mTOR inhibitor, was used as a standard compound for the comparative analysis. Computational docking approach was performed, using AutoDock Vina (screening) and AutoDock 4.2.6 (analysis). Based on our analysis, asiaticoside and its derivative, asiatic acid, both from Centella asiatica, revealed optimum-binding affinities with mTOR that were comparable to our standard compound. The effect of asiaticoside and asiatic acid on mTOR inhibition was validated with UMB1949 cell line, and their IC50 values were 300 and 60 µM, respectively, compared to everolimus (29.5 µM). Interestingly, this is the first study of asiaticoside and asiatic acid against tuberous sclerosis complex (TSC) disease model by targeting mTOR. These results, coupled with our in silico findings, should prompt further studies, to clarify the mode of action, safety, and efficacy of these compounds as mTOR inhibitors.
Stem cells from human exfoliated deciduous teeth (SHED) and dental pulp stem cells (DPSCs) obtained from the dental pulp of human extracted tooth were cultured and characterized to confirm that these were mesenchymal stem cells. The proliferation rate was assessed using AlamarBlue® cell assay. The differentially expressed genes in SHED and DPSCs were identified using the GeneFishing™ technique. The proliferation rate of SHED (P < 0.05) was significantly higher than DPSCs while SHED had a lower multiplication rate and shorter population doubling time (0.01429, 60.57 h) than DPSCs (0.00286, 472.43 h). Two bands were highly expressed in SHED and three bands in DPSCs. Sequencing analysis showed these to be TIMP metallopeptidase inhibitor 1 (TIMP1), and ribosomal protein s8, (RPS8) in SHED and collagen, type I, alpha 1, (COL1A1), follistatin-like 1 (FSTL1), lectin, galactoside-binding, soluble, 1, (LGALS1) in DPSCs. TIMP1 is involved in degradation of the extracellular matrix, cell proliferation and anti-apoptotic function and RPS8 is involved as a rate-limiting factor in translational regulation; COL1A1 is involved in the resistance and elasticity of the tissues; FSTL1 is an autoantigen associated with rheumatoid arthritis; LGALS1 is involved in cell growth, differentiation, adhesion, RNA processing, apoptosis and malignant transformation. This, along with further protein expression analysis, holds promise in tissue engineering and regenerative medicine.
Background: Betel quid chewing is more common among the older generation in rural areas of Malaysia. Oral cancer in Asia has been associated with the habit of chewing betel quid and areca nut. Objective: This study aims to investigate the cytotoxic effects of betel quid and areca nut extracts on the fibroblast (L929), mouth-ordinary-epithelium 1 (MOE1) and oral squamous cell carcinoma (HSC-2) cell lines. Methods: L929, MOE1 and HSC-2 cells were treated with 0.1, 0.2 and 0.4 g/ml of betel quid and areca nut extracts for 24, 48 and 72 h. MTT assay was performed to assess the cell viability. Results: Both extracts, regardless of concentration, significantly reduced the cell viability of L929 compared with the control (P<0.05). Cell viability of MOE1 was significantly enhanced by all betel quid concentrations compared with the control (P<0.05). By contrast, 0.4 g/ml of areca nut extract significantly reduced the cell viability of MOE1 at 48 and 72 h of incubation. Cell viability of HSC-2 was significantly lowered by all areca nut extracts, but 0.4 g/ml of betel quid significantly increased the cell viability of HSC-2 (P<0.05). Conclusion: Areca nut extract is cytotoxic to L929 and HSC-2, whereas the lower concentrations of areca nut extract significantly increased the cell viability of MOE1 compared to the higher concentration and control group. Although betel quid extract is cytotoxic to L929, the same effect is not observed in MOE1 and HSC-2 cell lines. Further investigations are needed to clarify the mechanism of action.
An ideal endodontic filling material should maintain a hermetic seal in the pathway of communication between the root canal and its surrounding tissues. [1] It should be biocompatible, dimensionally stable, exhibit favorable host tissue response, insoluble in tissue fluids, nontoxic, noncarcinogenic, and radiopaque. [2] Mineral trioxide aggregate (MTA) is an endodontic material first introduced as a root-end filling material in 1993. [3] It is composed of tricalcium silicate, tricalcium oxide, silicate oxide, and other mineral oxides. MTA exhibits many advantageous properties including optimum biocompatibility, good sealing ability, and favorable hard-tissue induction [4,5] which paved the way for its use in pulp capping, root-end filling, repairing furcal perforations, and resorption defects. [6,7] Despite favorable properties, white MTA (WMTA) has extended setting time, difficult handling properties, and discoloration potential and it is an expensive material. [8] Bismuth oxide (BO) is the radiopacifying agent in WMTA, and studies showed that BO negatively affects the physiochemical and biological properties, can interact with collagen in hard tissue, causes coronal discoloration, and can react with sodium hypochlorite. [9,10] WMTA is a Portland cement (PC)-based material, and therefore, white PC (WPC) was suggested as a viable substitute for
Betel quid chewing is a detrimental recreational habit amongst Asians and a risk factor for oral cancer. Arecoline, a component of areca nut (a major constituent of betel quid) is a known carcinogen. However, the effect of areca nut crude extract is not much studied. To evaluate the cytotoxicity and morphologic effects of areca nut aqueous extract on mouse fibroblast cell line (L929). Dried raw areca nut obtained from a local market in Kota Bharu, Kelantan was prepared and suspended in DMEM (Dulbecco’s Modified Eagle’s medium), prior to serial dilution of 1.56, 0.781, 0.39, 0.195, 0.0976, 0.0488, and 0.0244 mg/ml. The L929 was then exposed to each of the aqueous areca nut extract dilutions and incubated at 37 °C for 24, 48 and 72 hours. Following incubation, the cytotoxicity level of treated L929 was measured using MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium] assay. Five highest concentrations of areca nut extract showed significantly decreased L929 cell viability (1.56, 0.781, 0.39, 0.195, 0.0976 mg/ml) for all incubation periods compared to untreated cells (p<0.05). The IC50 values of aqueous areca nut extract on L929 were 0.1516, 0.1040, and 0.09136 mg/ml at 24, 48 and 72 hours, respectively. The L929 cell showed altered morphology when cultured in the extract for 24 hours. Higher concentrations of the areca nut aqueous extract is cytotoxic to L929. Prolonged exposure to the extract reduced the IC50 value. Investigation on the role of areca nut in cell proliferation could be further undertaken to assess its association with oral cancer. Keywords: areca nut, L929, mouse fibroblast cell line, cytotoxicity, MTT assay
This study aimed to evaluate the in vitro cytotoxic effects of locally produced processed natural coral (PNC) using human osteoblasts (HOS). Cytotoxicity was not observed when HOS cells were cultured with PNC, as assessed by (3-(4,5-dimethylthiazol-2-yl)-2-5-diphenyl tetrazolium bromide; MTT) and Neutral Red (NR) assays at concentration up 200 mg/mL for up to 72 hours. Flow cytometry (FCM) analysis showed that PNC (200 mg/mL) did not decrease viability of HOS cells after 48 and 72 hours of treatment. In a cell attachment study, the HOS cells attached to the edge of the PNC disc, and later grew into the pores of the PNC disc. All results from these studies indicate that locally produced PNC material is noncytotoxic and favors the growth of HOS cells.
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