One of the main chemotherapy agents for colon cancer is 5-fluorouracil (5-FU). However, the effectiveness of 5-FU decreased; therefore, co-chemotherapy with another agent is needed to enhance the ...activity. This study aims to determine the effect of red ginger extract as a co-chemotherapy agent with 5-FU on WiDr colon adenocarcinoma cells. We investigated the cytotoxic activity of the ethanolic extract of rhizome red ginger and combination with 5-fluorouracil (5-FU) in WiDr human colorectal cancer cell line. Red ginger extract was extracted by using 96% ethanol. Cytotoxic assay of red ginger extract and 5-FU was performed using MTT assay for 24 and 48 hours. Treatment of 5-FU in WiDr cells for 48 hours showed an IC50 value of 130 µg/mL, while no IC50 value was obtained for the 24 hours treatment. Treatment of red ginger extract with an incubation time of 24 and 48 hours had a cytotoxic effect on WiDr cells with IC50 values of 68 µg/mL and 65 µg/mL, respectively. The combination of 1000 μg/mL 5-fluorouracil with 35 μg/mL red ginger extract at 24-hour incubation resulted in a smaller cell viability value than every single treatment. The combination treatment of 5-FU 60 μg/mL with red ginger extract at a 25 μg/mL concentration causes a more significant decrease in cell viability than a single 5-FU treatment. In conclusion, red ginger extract may increase the cytotoxic activity of 5-FU in colon adenocarcinoma WiDr cells.
Active compounds as therapeutic agents are mainly found in natural products. Kaempferia pandurata from Kaempferia Genus has been used for the treatment of diseases. K. pandurata contains kaempferol ...(KMP) which exhibits various biological activities such as anticancer. KMP correlates to death-associated protein kinase 1 (DAPK1) relates to tumor suppression and apoptotic and autophagy mediation. This research aims to evaluate the anticancer potential of kaempferide (a methylated KMP at the C4’ position) against DAPK1 in silico. The research was performed through molecular docking to DAPK1 (5AUX and 5AV3), anticancer activity prediction, drug-likeness analysis, and ADMET (absorption, distribution, metabolism, excretion, and toxicology) evaluation. The binding affinity of kaempferide was -8.0 kcal/mol for 5AUX and 5AV3, respectively. The highest anticancer activity of kaempferide was shown against the prostate carcinoma cell line CWR22R. Kaempferide showed no violation to Lipinski-Veber rule and had good ADMET profile. Keywords: in silico, anticancer, kaempferide Senyawa aktif dengan potensi terapeutik banyak ditemukan dalam bahan alam. Kaempferia pandurata dari genus Kaempferia telah digunakan dalam pengobatan berbagai penyakit. K. pandurata mengandung kaempferol (KMP) dengan aktivitas biologis beragam, salah satunya adalah antikanker. KMP juga dapat berikatan dengan death-associated protein kinase 1 (DAPK1) yang berhubungan dengan penekanan tumor dan mediasi apoptosis dan autofagi. Penelitian ini mempelajari potensi antikanker kaempferida (KMP yang termetilasi pada posisi C4’) terhadap DAPK1 secara in silico. Penelitian dilakukan melalui penambatan molekular terhadap DAPK1 (5AUX dan 5AV3), perkiraan aktivitas antikanker, analisis drug-likeness, dan prediksi ADMET (absorption, distribution, metabolism, excretion, and toxicology). Afinitas ikatan kaempferida masing-masing sebesar -8,0 kkal/mol untuk 5AUX dan 5AV3. Aktivitas antikanker tertinggi kaempferida ditunjukkan terhadap cell line karsinoma prostat CWR22R. Kaempferida tidak melanggar aturan Lipinski-Veber sesuai analisis drug-likeness dan memiliki profil ADMET yang cukup baik. Kata kunci: in silico, antikanker, kaempferida
CD59 is a major inhibitor of membrane attack complex (MAC) formation, which is anchored to the cell membrane by glycosylphosphatidylinositol (GPI). The protein is widely expressed in most human ...tissues. Several studies have reported the involvement of CD59 with several diseases such as paroxysmal nocturnal hemoglobinuria (PNH), cancer, peripheral demyelination, multiple sclerosis, diabetes mellitus, and viral infections. Herein, we summarized the biological structure and expression pattern of CD59, and its biological function, and focused on discussing the involvement of CD59 in several diseases and its potential for therapeutic use.
•CD59 regulates immune system and protects cells from complement system.•CD59 deficiency is associated with paroxysmal nocturnal hemoglobinuria (PNH).•CD59 is implicated in cancer, autoimmune disorders, and diabetes mellitus.•CD59 has potential as a target for drug action.
Background: Two mangostin compounds, gamma-mangostin and alpha-mangostin, show anticancer properties through the inhibition of cell proliferation and cell migration. Metastatic triple-negative breast ...cancer (TNBC) cells, including MDA-MB-231, highly express C-X-C chemokine receptor type 4 (CXCR4) to maintain reactive oxygen species (ROS) and cell migration. Objectives: This study was performed to analyze and compare different modes of action of γ-mangostin and α-mangostin as antimigratory effects targeted on CXCR4 in MDA-MB-231 as a model of TNBC cell. Methods: This study investigated the effect of γ-mangostin and α-mangostin using a series of assays, including Cell Counting Kit-8 (CCK-8) assay for cytotoxicity, wound healing assay for migration study, quantitative real-time polymerase chain reaction (qRT-PCR) for gene expression analysis, and flow cytometry for ROS measurement, along with in silico study to observe the binding between the compound and CXCR4. Results: The findings revealed half maximal inhibitory concentration (IC50) values of 25 and 20 μM for γ-mangostin and α-mangostin in MDA-MB 231 cells, respectively. Moreover, a concentration of 10 μM was used for the migration assay. Both γ-mangostin and α-mangostin significantly suppressed cell migration within 24 hours. The present gene expression studies revealed the downregulation of key migration-associated genes, namely Farp, CXCR4, and LPHN2, upon γ-mangostin treatment but not α-mangostin. Additionally, both γ-mangostin and α-mangostin increased cellular ROS generation, highlighting the same effect of γ-mangostin and α-mangostin ROS elevation to inhibit cancer cell migration. Molecular docking simulations further suggested a potential interaction between γ-mangostin and α-mangostin with CXCR4 in high affinity. Conclusions: These findings suggest that both γ-mangostin and α-mangostin inhibit breast cancer cell migration and induce cellular ROS levels in MDA-MB-231 cells; notably, γ-mangostin suppresses CXCR4 mRNA expression that might correlate to its activity to inhibit MDA-MB-231 cell migration.
Breast cancer is a second deadly cancer after lung cancer worldwide. Progression of cancer is driven by mutated cancer drive gene such as ARHGAP35. This study aims to analyze the role of ARHGAP35 in ...the growth and development of breast cancer cells. ARHGAP35 expression level was analyzed using Oncomine (p-value<1E-4; gene rank top 10%). Overall survival (OS) and disease-free survival (DFS) were evaluated by using GEPIA (median cutoff; HR displayed with 95% CI). STRING was used for analyzing the protein-protein interaction network, while WEBGESTALT for KEGG pathway and gene ontology (GO) of ARHGAP35 and associated proteins and cBioPortal for gene mutation. ARHGAP35 was overexpressed in several types of breast cancer, namely invasive ductal breast carcinoma (IDC), invasive ductal and lobular breast carcinoma (IDLC), invasive lobular breast carcinoma (ILC), male breast carcinoma, and mixed ductal and lobular carcinoma (MDLC). High expression of ARHGAP35 had significantly lower OS (p=0.045) compared to low expression of ARHGAP35 and the difference in DFS was not significant (p=0.98). ARHGAP35 interacted with RHOA, RHOB, RHOC, RHOD, RASA1, RND1, RAC1, CDC42, FYN and SRC. KEGG pathway and GO analysis showed that these proteins are highly involved in actin-based processes through adherent junction, axon guidance, focal adhesion, regulation of actin cytoskeleton, and tight junction. Mutation rate analysis showed 34 missense, 29 truncating, 3 fusion, and 1 in frame on ARHGAP35. Taken together, ARHGAP35 may involve in the growth and development of breast cancer through regulation of actin cytoskeleton pathway.Keywords: ARHGAP35, breast cancer, KEGG pathway, mutation rate, actin cytoskeleton.
The prevalence of degenerative diseases increases with age. Furthermore, various factors tend to trigger cells injury, thereby, causing inflammation. This study, therefore, aims to examine the ...anti-inflammatory mechanisms of steeping date seeds in middle age women. This is a quasi-experimental design with a pre- and post-test approach used to evaluate the anti-inflammatory effect of 2.5 g of steeped of date palm seed, consumed by 30 healthy middle-aged women per day (in 250 mL water) for 14 days. The final numbers (22 subjects) of recruited women were included in the statistical analysis. Their level of IL-1β, TGF-β, IL-6, TNF-α, IL-12, COX-1, COX-2, and PGE2 were determined using ELISA. The results showed that the expression of IL-1β, TGF-β, COX-1, and COX-2 in women significantly decreased after consuming date palm seed. Steeped of date seed acts as an anti-inflammatory by downregulating the expression of key proinflammatory mediators.
Calophyllum soulattri (Sulatri), a plant from Clusiaceae family, has been empirically used as traditional medicine. In the present study, C. soulattri stem bark extract and fractions were evaluated ...for their toxicity against MCF-7 breast cancer cell. The extract and fraction’s chemical content was analyzed using the combination of liquid chromatography with mass spectrometry (LC-MS/MS). The results showed that methanol extract and n-hexane fractions have strong cytotoxic activity with IC50 values 93.6 and 36 µg/mL, respectively. Meanwhile, as the positive control, ethyl acetate and cisplatin fractions have IC50 values 233 and 16.2 µg/mL, respectively. The LC-MS/MS analysis showed that the extract and fractions contained polyporusterone A, poricoic acid D, polyporusterone F, esulentagenin, and 1-acetyl-3-(methoxy-carbonyl)-β-carboline. Therefore, C. soulattri stem bark extract and fractions have potential activity as an anticancer agent that was able to inhibit MCF-7 breast cancer cell growth.
Morusin, an active constituent of the mulberry plant (Morus alba), exhibits inhibitory effects on several types of cancer cells in vitro, including breast cancer. This study aimed to identify ...potential target proteins of morusin, investigate the binding energy, and explore type of interactions between morusin and the target protein. Morusin target was searched using the PubMed, STITCH, STRING, and Cytoscape databases. Subsequently, the obtained morusin target protein data underwent processing using Autodock Tools and DS BIOVIA to facilate the simulation of molecular docking between morusin and the target protein. The study identified EGFR, SRC, and MAPK1 as potential targets for morusin. Docking simulations revealed that both EGFR and SRC represent viable targets for morusin, as their binding energies were lower than those of the native ligand and lapatinib. Specifically, the bond energies at EGFR were -9.6, -7.5, and -9.2 kcal/mol for morusin, the native ligand, and lapatinib, respectively. Similarly, at SRC, the corresponding bond energies were -8.2, -6.4, and -5.3 kcal/mol. Morusin demonstrated binding interactions with Leu694, Val702, Leu820, Ala719, Leu768, and Lys721 at the active site of EGFR, and with Lys295 and Gly344 at the binding active sites of SRC. Consequently, morusin has the potential to suppress cancer cell growth by targeting EGFR and SRC.Keywords: cancer cells, EGFR and SRC as targets, molecular docking, morusin, mulberry plant.
The expression of COX-2 and iNOS have an important role in inflammation. Turmeric (Curcuma domestica) contains active compounds such as curcumin, which can inhibit the expression of the enzyme so ...that the risk of chronic inflammation and cancer can be reduced. The aim of this study was to determine the anti-inflammatory effects of turmeric extract concentrations on the expression of COX-2 and iNOS in RAW 264.7 cells induced by lipopolysaccharide (LPS). This study was an experimental post-test only with a control group design. The RAW 264.7 cultured cells were divided into six groups (G) on a 24-well plate; GA (control group without LPS), GB (control group with LPS), GC (control group without primary antibody), GD (62,5μg/mL extract concentration), GE (125μg/mL extract concentration), and GF (250μg/mL extract concentration). After 18 hours of treatment, all the cells were fixed with ethanol and stored and tested with immunocytochemistry. Results show the expressions of COX-2 and iNOS in GA (10,51±5,15; 12,51±3.10), GB (82,29±1,49; 82,70±1,67), GC (29,01±5,19; 16,33±1,61), GD (32,19±5,36; 58,58±10,31), GE (24,29±5,88; 52,55±9,03), and GF (40,42±3,15; 29,24±7,84). The test results of data analysis by one-way ANOVA (COX-2) and Kruskal-Wallis (iNOS) showed significant differences (p <0.05) along with Post Hoc test Tamhanes (COX-2) and Mann-Whitney (iNOS), which also showed significant differences (p <0.05). The most substantial differences shown by the mean of the treatment group turmeric extract concentration were 125 μg/mL (COX-2) and 250μg/mL (iNOS). These results suggest that turmeric extracts can reduce the effects of inflammation on RAW 264.7 cells induced by lipopolysaccharide
Black solo garlic (BSG) has been evaluated for its ability to reduce free radicals; however, the safety test on kidney and liver function has not been evaluated. This study aimed to examine the ...effect of brewed BSG on the liver (total protein, albumin, glutathione S-transferase/GST) and kidney (urea, creatinine, and β
-microglobulin) function in streptozotocin (STZ)-induced white rats. The experimental animals were randomly divided into six groups, each including five animals. The groups consist of the normal control group, the STZ-induced control group, the BSG treatment group with doses 6.5, 13.5, and 26 g/kg body weight, and metformin positive control. After STZ induction, the serum levels of GST, total protein, and albumin are decreased. After treatment with BSG, the serum level of GST, total protein, and albumin increased significantly (
< 0.05). The levels of urea, creatinine, and β
-microglobulin increased after STZ induction. After treatment of BSG, levels of urea, creatinine, and β
-microglobulin are decreased significantly (
< 0.05). These results suggest that BSG use is safe for the liver and kidneys of STZ-induced rats.
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