Changed synapse density has been suggested to be involved in the altered brain connectivity underlying schizophrenia (SCZ) pathology. However, postmortem studies addressing this topic are heterogeneous and it is not known whether changes are restricted to specific brain regions. Using meta-analysis, we systematically and quantitatively reviewed literature on the density of postsynaptic elements in postmortem brain tissue of patients with SCZ compared to healthy controls. We included 3 outcome measurements for postsynaptic elements: dendritic spine density (DSD), postsynaptic density (PSD) number, and PSD protein expression levels. Random-effects meta-analysis (31 studies) revealed an overall decrease in density of postsynaptic elements in SCZ (Hedges’s g : −0.33; 95% CI: −0.60 to −0.05; P = .020). Subgroup analyses showed reduction of postsynaptic elements in cortical but not subcortical tissues (Hedges’s g : −0.44; 95% CI: −0.76 to −0.12; P = .008, Hedges’s g : −0.11; 95% CI: −0.54 to 0.35; P = .671) and specifically a decrease for the outcome measure DSD (Hedges’s g : −0.81; 95% CI: −1.37 to −0.26; P = .004). Further exploratory analyses showed a significant decrease of postsynaptic elements in the prefrontal cortex and cortical layer 3. In all analyses, substantial heterogeneity was present. Meta-regression analyses showed no influence of age, sex, postmortem interval, or brain bank on the effect size. This meta-analysis shows a region-specific decrease in the density of postsynaptic elements in SCZ. This phenotype provides an important cellular hallmark for future preclinical and neuropathological research in order to increase our understanding of brain dysconnectivity in SCZ.
Studies have shown that algae and seaweed have cytotoxic activity. This study was aimed to determine the cytotoxic activity of Spirulina platensis and Ulva compressa Linn. extracts against cancer cell lines. The cytotoxic activity of the extract was carried out using the MTT ((3-(4,5-dimetylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) method. Results showed that the ethanol extract and methanol extract of Spirulina platensis have no cytotoxic effect against HeLa, WiDr, MCF7 and T47D cells. Water extract of Spirulina platensis had no cytotoxic activity on T47D and Vero cells. Water extracts of Spirulina platensis increase MCF7 cell growth. Phycocyanin powder also stimulates MCF7 cell growth. Ethanol extract of Ulva compressa Linn. exhibited potentially cytotoxic activity against MCF7 and moderate cytotoxic against WiDR cells with IC50 values are 31.86 μg/ mL and 104.93 μg/mL, respectively. It can be concluded that extract of Spirulina platensis has no potential to be developed for cancer therapy. Ulva compressa Linn has the potential to be developed as an anti-cancer. Further research for study the mechanism of anticancer of Ulva compressa Linn on MCF7 was needed.
Previous research has shown that some compounds in leaves and seeds of sugar apple have a cytotoxic activity. The aim of this research was to determine the cytotoxicity of semipolar fraction of ethanolic extract from sugar apple stem bark (Annona squamosa L.) on T47D cancer cells. The semipolar fraction of ethanolic extract from sugar apple stem bark was collected by fractionation using Vacuum Liquid Chromatography (VLC) with hexane:ethyl acetic (9:1, 8:2, 7:3, and 6:4) as mobile phase. Cytotoxicity from the fractions of five different concentration namely; 25, 50, 100, 150, and 250, µg/mL was measured by MTT assay. The potency of the cytotoxicity was defined by the ability of the fraction to inhibit the growth of T47D cells indicated by the value of IC50. Qualitative analysis of contained compounds in the fraction was done by Thin Layer Chromatography (TLC) method using silica gel F 254 as a stationary phase and hexane:ethyl acetic (7:3) as a mobile phase. UV 254 and 366 nm lamp also Dragendorff, citroboric, and FeCl3 spray reagents were used to visualize the spots of the secondary metabolites. The result proved that the semipolar fraction of ethanolic extract from sugar apple stem bark showed potential cytotoxicity on T47D cancer cells with IC50value of 70,77 µg/mL. Qualitative analysis showed that the fraction contained flavonoids and alkaloids which is presumably responsible for its cytotoxic activity.
Cervical cancer was the fourth-highest incidence of female cancer globally in 2020 and the second-highest incidence of female cancer in Indonesia in 2019. Chemotherapy frequently causes side effects and resistance; thus, cancer therapeutic agents must be developed to find selective anticancer drugs. One of the plants that has the potential as an anticancer agent is soursop. Soursop seed extract demonstrated anticancer activity, but research on soursop seed protein has never been published. This research aims to determine the cytotoxicity of soursop seed protein (Annona muricata L.) isolated using DEAE matrix against HeLa and Vero cells. Soursop seeds were extracted by adding 0.14 M NaCl at 4 °C in 5 mM sodium phosphate buffer pH 7.2. Protein purification was done by ion-exchange column chromatography with stationary phase DEAE matrix and mobile phase NaCl ranging from the lowest molarity of 0.2 M to the highest molarity of 0.4 M. Protein fraction concentrations were measured using Biodrop at A260/280. MTT assay was employed to test the cytotoxic activity of protein fraction soursop seed, followed by measurement of cells' metabolic activity with ELISA reader at λ 550 nm. The results of protein isolation showed that the highest concentration of protein fraction eluted 0.2 M NaCl were 8466.2 μg/mL; 8346.4 μg/mL; 8205.0 μg/mL; and 8284.0 μg/mL. Cytotoxic tests using soursop seed protein with the concentrations of 32.2 μg/mL; 16.1 μg/mL; 8.05 μg/mL; and 4.025 μg/mL respectively resulted in 114.436%; 116.822%; 117.776%; and 119.526% HeLa cell survival. Meanwhile, isolated proteins with the concentration of 23.7 g/mL; 11.85 g/mL; 5.925 g/mL; and 2.9625 g/mL respectively resulted in 90.671%; 115.284%; 123.025%; and 127.590% of Vero cell survival. In conclusion, soursop seed protein did not possess cytotoxic activity against HeLa and Vero cells.
Melinjo seeds are one of the plants that have the potential to be developed as anticancer drugs. This study aimed to determine the cytotoxic activity of melinjo seed protein against MCF-7 and vero cells, and to determine the antiproliferative activity of melinjo seed protein against MCF-7 cells. The method used for the isolation of melinjo seed protein was SDS-PAGE. Cytotoxic and antiproliferative activities were carried out using the MTT assay method and the absorbance was read on an ELISA reader. The results showed that melinjo seed protein had cytotoxic activity against MCF-7 cells with IC 50 of 125.89 μg/mL. The IC 50 results of melinjo seed protein against vero were 3.37 μg/mL. Melinjo seed protein was not selective against vero cells where the SI values were 0.03. In the antiproliferative activity test of melinjo seed protein, the doubling time at levels of 1.875 μg/mL was 86.55 h, while the control cell doubling time was 112.32 h. These results indicated that melinjo seed protein was not able to inhibit the proliferation of MCF-7 cells.
One of the new anticancer treatments that can be developed is a protein similar to RIPs. RIP is an enzyme found in various parts of plants that is toxic and can inhibit protein synthesis. Soursop seeds (Annona muricata L.) may be developed into anticancer. The plant of the same genus, Annona Squamosa L., has been proven to have a protein content similar to that of RIPs because it can supercoil DNA into circular nicks at low levels. Another study reported that soursop seed protein had moderate cytotoxic activity against 4T1 cells but did not show any antiproliferative activity. This study was conducted to determine the cytotoxic and antiproliferative activity of soursop seed (Annona muricata L.) protein against MCF-7 cells. Cytotoxic and antiproliferative activity tests were carried out using the MTT method on the protein fraction of soursop seeds. Cytotoxicity test was performed within 24 h. The antiproliferative test was carried out for 24, 48, and 72 h with the test parameter, doubling time. The results of the cytotoxicity test obtained that the protein fraction had weak cytotoxic activity with an IC 50 value of 429,90 μg /mL. The antiproliferative results implied that there was no growth inhibition as indicated by the concentration of the protein fractions of 7,5 μg/mL and 3,75 μg/mL, which were unable to prolong the time twice compared to control cells. The results of this study showed that the protein fractions of soursop seeds did not have antiproliferative activity against MCF-7 cells.
The plant protein of melinjo (Gnetum gnemon) in seeds is known to have antioxidant properties. Apart from being an antioxidant, melinjo seed protein also has the potential to be developed as an anticancer compound. One of the potential anticancer compounds has been screened based on supercoiled DNA cleavage activity (pBSKS). The purpose of this study was to determine the activity of the protein fraction isolated with DEAE and BUTYL matrices against supercoiled DNA cleavage of pBSKS. Supercoiled DNA cleavage test activity of pBSKS was determined using the electrophoresis method and visualized with a UV transilluminator at a wavelength of 312 nm. The cytotoxic activity of melinjo seeds was tested through the MTT assay method and was read on an ELISA reader with a wavelength of 550 and 595 nm seen from the IC50 value. The protein fraction of melinjo seeds isolated with DEAE and BUTYL matrices had concentrations of 470.1 and 81.02 g/mL, respectively. The visualization results showed that the DEAE and BUTYL protein fractions resulted in depletion of supercoiled DNA bands of pBSKS. The concentration of active protein in the melinjo seeds fractionated using the DEAE-650M matrix was higher than that of the BUTYL-650M matrix. In this study, after several cytotoxic tests were carried out, various results were obtained. The activity of protein isolates from melinjo seeds fractionated using DEAE-650M and BUTYL-650M against 4T1 and T47D cells could be categorized as non-toxic because the IC50 value was > 1000 g/mL and the average percentage of viable cells was more than 50%, except for the seed protein fraction. Melinjo fractionated using DEAE-650M against T47D cells which had an IC50 value of 127.62 g/mL could be categorized as quite active and cytotoxic. Keywords: Gnetum gnemon L., protein isolation, ribosome-inactivating proteins (RIPs), DNA cleavage, cytotoxic, T47D, 4T1
Melinjo (Gnetum gnemon L.) is an easily discovered plant in Indonesia. The previous researchers documented that the Melinjo seed has anticancer activity. This plant contains a high concentration of Ribosome Inactive Proteins (RIPs), which could inhibit protein synthesis. The research aims to determine the cytotoxic and antiproliferative activity of Melinjo seed extract against cervical cancer (HeLa) and breast cancer (4T1) cell lines. The extract was collected using the ion exchange DEAE matrix isolation method. The bioactivity test was done by MTT assay. The cytotoxic activity was determined by the IC 50 value of 361,1 µg/mL and 939,723 µg/mL against 4T1 and HeLa cells, respectively. The antiproliferative activity was determined by doubling the time value on the concentration of 15 µg/mL and 7,5 µg/mL at 24, 48, and 72 h of the test. The result showed no inhibition activity of the extract because the doubling time of the control cells group was higher than the tested group. It can be concluded that the protein fraction of Melinjo seed does not have the cytotoxic and antiproliferative activities against HeLa and 4T1 cell lines.
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