Indonesian Journal of Cancer Chemoprevention
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Protein-protein Docking Studies of Estrogen Receptor Alpha and TRIM56 Interaction for Breast Cancer Drug Screening
Full text linkBreast cancer is the highest mortality cause in women with cancer. Protein-protein docking for target-based screening is an effective approach in breast cancer drug discovery via estrogen receptor (ER) signaling. TRIM56, an E3 ubiquitin protein ligase, can bind to and stabilize ER alpha. Thus, drug screening that can inhibit or weaken the interaction between ER alpha and TRIM56 is promising to obtain novel yet specific breast cancer drugs. In this study, we performed protein-protein docking studies for ER alpha and TRIM56 interaction and virtual screening for FDA-approved drugs from the ZINC database against ER alpha and TRIM56 complex protein model structure. We utilized Cluspro 2.0, PyRx 0.8, and Pymol 2.4.1 to conduct protein-protein docking, virtual screening, and model structure visualization. PIP and PLIP software were also applied to analyze the amino acid residue between proteins or protein-ligands. Based on the protein-protein docking, ER alpha and TRIM56 established interaction. Utilizing this complex protein as a macromolecule in the virtual screen of 1071 molecules of FDA-approved drugs, we obtain the top five lowest binding energy molecules i.e., dutasteride, dihydroergotamine, nilotinib, ergotamine, and bromocriptine. In addition, the energy binding affinity between ER alpha-dutasteride complex with TRIM56 was weakened in the presence of dutasteride. In conclusion, protein-protein docking between ER alpha-TRIM56 was able to select FDA-approved drugs that could bind to the complex, and dutasteride binding to ER alpha-TRIM56 complex weakened the interaction.Keywords: protein-protein docking, estrogen receptor alpha, TRIM56, breast cancer, ubiquitin
Dosimetric Comparison between Intensity Modulated Radiation Therapy (IMRT) and Three-Dimensional Conformal Radiation Therapy (3DCRT) in Mid Lower esophageal Carcinoma: An Analytical Observational Study
Full text linkEsophageal cancer (EC) is a common cancer with high mortality because of its rapid progression and poor prognosis. One of the most successful therapies for EC is radiotherapy. Two recently created radiation methods are intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3D-CRT). In terms of target coverage, dose homogeneity, and lowering toxicity to healthy organs, IMRT is thought to be superior to 3D-CRT. These benefits haven't been proven in the treatment of EC, though. This study was performed to investigate if intensity modulated radiation therapy (IMRT) offers a better planning target volume (PTV) coverage and/or lower dose to organs at risk in comparison to three-dimensional conformal radiation therapy (3DCRT). 30 patients with locally advanced histo-pathologically proven mid and lower oesophageal carcinoma, not reaching gastro-esophageal junction were treated with chemoradiation using IMRT technique. 3DCRT plans were generated for those 30 patients. The IMRT and 3DCRT plans were compared in terms of PTV coverage and doses to organs at risk. Our results revealed that IMRT is better than 3DCRT comparing PTV coverage and doses to organs at risk having statistically significant difference between both techniques (p<0.001). As for the organs at risk (OAR), the V20 for the IMRT plans delivered lesser lung volume irradiation also the mean dose to the heart and the V30 were both higher in the 3DCRT plans.Keywords: esophageal cancers (ECs), Organs at risk (OAR), Intensity modulated radiation therapy (IMRT), Three-dimensional conformal radiation therapy (3DCRT), Planned target volume (PTV)
Simple Procedure for the Isolation of Mesenchymal Stem Cells from Different Parts of the Human Umbilical Cord
Full text linkThe umbilical cord and placenta are both sources of mesenchymal stem cells (MSCs) that are promising for cell-based therapy. Furthermore, compared to other MSCs sources, they are easy to obtain with no invasive procedures. This study presents an adapted method for stem cell isolation from three different parts of the human umbilical cord, including Wharton’s jelly (WJ), cord lining (CL), and cord-placenta junction (CPJ). The isolation consists of sample preparation, tissue dissection into distinct anatomical regions, mincing and enzyme digestion, and explant culturing. In addition, we monitored when the cells migrated from the explant to the bottom of the cell culture dish and passed the cells after they became confluent. This study found that WJ cells were the first to reach confluence at Passage 0 (P0). In contrast, CL cells needed the longest time to get confluence at P0 but displayed faster cell growth after subsequent passages (P1-P2). In addition, CPJ cells showed growth retardation after P1 and P2. Altogether, we could extract the MSCs from umbilical cord tissue explants by using DMEM supplemented with 10% FBS, 100 IU/mL penicillin, and 100 μg/mL streptomycin as general cell culture medium and omitting the use of gentamicin. However, the MSCs may need a more complex specified medium for optimum cell regeneration for further cell expansion.Keywords: mesenchymal stem cells, umbilical cord, Wharton’s jelly, cord lining, cord-placenta junction
Potential Inhibition of Melaleuca leucadendron L. Compounds Against the NSP5 SARS CoV-2 Protein
Full text linkCOVID-19 is an infectious disease caused by Severe Acute Respiratory Syndrome (SARS-CoV-2), causing a global health emergency as a pandemic disease. The lack of certain drug molecules or treatment strategies to fight this disease makes it worse. Therefore, effective drug molecules are needed to fight COVID-19. Non Structural Protein (NSP5) or called Main Protease (Mpro) of SARS CoV 2, a key component of this viral replication, is considered a key target for anti-COVID-19 drug development. The purpose of this study is to determine whether the compounds in the Melaleuca leucadendron L. plant such as 1,8-cineole, terpene, guaiol, linalol, α-selinenol, β-eudesmol and γ-eudesmol are predicted to have antiviral activity for COVID-19. Interaction of compounds with NSP5 with PDB code 6WNP analyzed using molecular docking with Molegro Virtual Docker. Based on binding affinity, the highest potential as an anti-viral is Terpineol with binding energy (-119.743 kcal/mol). The results of the interaction showed that terpinol has similarities in all three amino acid residues namely Cys 145, Gly 143, and Glu 166 with remdesivir and native ligand. Melaleuca leucadendron L. may represent a potential herbal treatment to act as: COVID-19 NSP5, however these findings must be validated in vitro and in vivo.Keywords: COVID-19, In Silico, NSP5/ 6WNP, Melaleuca leucadendron L
Antimigratory Evaluation from Curcumin-Derived Synthetic Compounds PGV-1 and CCA-1.1 on HCC1954 and MDA-MB-231 Cells
Full text linkEarlier findings reported the anticancer-mediated activities of curcumin-modified compounds Pentagamavunone-1 (PGV-1) and Chemoprevention Curcumin Analog 1.1 (CCA-1.1) with several mechanisms including cell cycle arrest, reactive oxygen species (ROS) production, and cell migration disruption. Our study aims to evaluate the antimigratory activity of PGV-1 and CCA-1.1 on aggressive breast cancer cell lines (MDA-MB-231 and HCC1954 cells) and their effect on HER2 protein. The trypan blue exclusion method was conducted for the antiproliferative effect. The PGV-1 or CCA-1.1 effect on cell migration was determined by wound healing assay. Using gelatin zymography, we checked the secretion level of matrix metalloproteinase (MMP). We also evaluated the human epidermal growth receptor-2 (HER2) level after incubation with PGV-1 or CCA-1.1 in HCC1954 cells by western blot. Based on the antiproliferation assay, MDA-MB-231 and HCC1954 cells were sensitive to PGV-1 and CCA-1.1. MMP-2 was only observed in HCC1954 cells while MMP-9 was only observed in MDA-MB-231. Both PGV-1 and CCA-1.1 significantly suppressed MMP-9 activity in MDA-MB-231 cells. Moreover, PGV-1 inhibited HER2 protein levels in HCC1954 although it was not significant, whereas CCA-1.1 did not affect HER2 protein. This study strengthens the scientific evidence for PGV-1 and CCA-1.1 activities for future exploration as candidate chemotherapy with multitarget against breast cancer.Keywords: Curcumin analog, cell migration, MMP-9, HER2, breast cancer
Clinical Profile and Treatment Outcome of Chordoma: A Tertiary Care Experience in North India
No full textChordoma is a slow growing cancer of tissue found inside the spine. Chordoma can happen anywhere along the spine. It is most often found near the tailbone (called a sacral tumor) or where the spine meets the skull (called a clival tumor). Chordoma is also called notochordal sarcoma. The main objective of this study was to determine the clinical profile and treatment outcome of chordoma patients. All the patients were diagnosed using radiological imaging and biopsy. The site of origin of chordoma was the sacrum in seventeen (71%) patients, the spine in six (25%) patients, and the skull base in one (4%) patient. 21 (88%) of the twenty-four patients received primary surgery. These 21 patients then received adjuvant radiation therapy using the intensity modulated radiation therapy (IMRT) strategy, with radiation dose ranging from 70Gy to 74Gy. Three patients (12%) did not undergo surgery; two had low performance status and received only radiotherapy; the third with the disease at the base of the skull was unresectable; this patient received radiotherapy first, then imatinib. Compared to individuals who get radiation alone, the addition of adjuvant radiation therapy to surgery in chordoma patients enhances overall survival.Keywords: chordoma, radiotherapy, targeted therapy
The Exploration of Vetiver (Vetiveria zizanioides) as Co-Chemotherapy of Lung Cancer Selectively Targets AKR1C1: Bioinformatics Approach
Full text linkReactive Oxygen Species (ROS) is one of the cancer-causing agents, one of which is lung cancer. In addition to being carcinogenic, ROS can also be used to kill cancer cells themselves, by increasing their levels to the threshold of apoptosis. Therefore, it is necessary to inhibit certain antioxidant enzymes that are highly expressed in lung cancer. One of them is AKR1C1 which plays a role in the eradication of intracellular ROS. However, AKR1C1 has a high structural similarity to AKR1C2, so it can inhibit therapy causing selectivity problems. Vetiver (Vetiveria zizanioides) has potential as an anticancer. This study was conducted to explore vetiver as a co-chemotherapeutic agent for lung cancer targeting AKR1C1 selectively. The method used is distillation, identification of vetiver compounds using GC-MS, and through bioinformatics studies. Predictive analysis with KNIME was carried out to determine the activity of the test compound. All tested vetiver compounds had a predictive value of 1 (active) on AKR1C1 and 0 (inactive) on AKR1C2. Through GC-MS obtained 354 compounds were identified. These compounds are used to filter the compounds predicted by KNIME. The molecular docking results showed that of the 10 tested vetiver compounds, there was 1 compound that had the strongest bond in interacting with AKR1C1, namely beta vetispirene compound with an S-score of -15.12 kcal/mol, and stronger than native ligand and aspirin. Based on the research data, it can be concluded that the beta vetispirene compound in vetiver can be a potential co-chemotherapy agent for lung cancer in targeting AKR1C1 selectively. However, further research is needed to prove its activity on lung cancer cells.Keywords: ROS (Reactive Oxygen Species), Lung Cancer, AKR1C1, selectivity, vetiver (Vetiveria zizanioides)
The Effectiveness of Topical 5-fluorouracil Treatment on Mouse Skin Squamous Cell Precancerous Lesions through Caspase-3 Expression
No full textSkin cancer is a disease that develops in the epidermis of the skin and can be invasive, such as squamous cell carcinoma (SCC). Early detection of squamous cell precancerous can prevent these lesions from progressing to invasive SCC and increase the effectiveness of therapy. 5-fluorouracil (5-FU) is an antimetabolite compound as a pyrimidine DNA/RNA antagonist molecule that induces cell apoptosis. The main objective of this study was to evaluate the effectiveness of the topical 5-FU cream (Dharmais NCH) compared to imiquimod 5% on apoptosis through the expression of caspase-3 in precancerous squamous cells of mouse skin induced by 7,12-dimethylbenzen[a]-anthracene (DMBA)/croton oil treatment. This research assess three differences concentration of 5-FU include 1%, 2%, and 5% on 24 wild type mouse divided into 6 groups including positive control (with carcinogenesis but without treatment), negative control (without treatment; normal), carcinogenesis with treatment 5-FU cream (1%, 2%, and 5%) or 5% imiquimod cream. Two-stages carcinogenesis induced by DMBA and followed by croton oil. The expression of caspase-3 was analyzed using immunohistochemistry. Statistical analysis was performed by one-way ANOVA using SPSS version 23. The induction of two-stages of carcinogenesis (weeks 1 to 10) caused papilloma lesions on the skin of mouse. Furthermore, 5-FU treatment for 4 weeks (weeks 11 to 14) showed a decrease in the cumulative number of papillomas (p0.05). The apoptotic effect of 5-FU treatment on precancerous skin squamous cell lesions in mouse was not significantly different from the standard treatment using imiquimod. This suggests that 5-FU treatment has potential as a future therapy in squamous cell precancerous skin lesions.Keywords: 5-fluorouracil, caspase-3, squamous cell precancerous, skin, topical treatment
Induction of Helianthus annuus Leaves Extract to HeLa cell Apoptosis and Cell Cycle Arrest in S, G2-M and M5 Phase
Full text linkHelianthus annuus L. (H. annuus) is a potential medicinal plant for cancer therapy. The aims of this study is to identify profile the anticancer activity of H. annuus L. from its leaves, root, stem, and seed as well as to elucidate the apoptosis and cell cycle of the leaves. Ten-gram sample of the powder were extracted by using Ultrasound-Assisted Extraction (UAE) with 200 ml of 96% ethanol by comparison of 1:20 with three times replications. The determination of anticancer activity was used the MTT cell proliferation assay, while apoptosis test and cell cycle were applied with the flowcytometry test. The value of IC50 in 96% ethanol extract in the root and stem was >1,000 μg/mL; seed and leaves were 153.76 μg/mL; and 126.6 μg/mL, respectively. The apoptosis induction of H. annuus leaves extract treatment was 7.17% of apoptosis cells; 90.44% of necrosis, and 2.39% of living cells. The H. annuus leaves extract also significantly caused a decrease of cell percentage in G0-G1 phase (p<0.001) and an increase in G2-M phase (p<0.001). The H. annuus leaves extract had greater potential as anticancer instead of other parts. The adding of H. annuus leaves extract increased the HeLa cell apoptosis, decreased percentage of HeLa cells in G0-G1 phase, and increased percentage of HeLa cells in G2-M phase. Cell cycle mechanism test showed cell cycle arrest in S, G2-M, and M5 phase in 24 h, hence inhibited the mitosis process.Keywords: anticancer, Helianthus annuus L, apoptosis, cell cycle
Cytotoxicity Effect of Self-Nanoemulsifying Drug Delivery System from Chloroform Extract of Bay Leaf (Syzygium Polyanthum (Wight) Walp.) with Oleic Acid as a Carrier
Full text linkBay leaves are used as food flavoring and also have medicinal properties. They may have cytotoxic effects derived from natural ingredients. The low efficacy of the therapy with an adequate dose preparation of the plant extract is due to its low solubility and oral bioavailability that is less than the maximum. Hence, this study aimed to improve the solubility and oral bioavailability of the extract mainly for the chloroform extract of leaves that are not soluble in water by preparing a self-nanoemulsifying drug delivery system (SNEDDS). Then, the potential cytotoxic effects of the SNEDDS of bay leaves were determined by calculating the value of IC50 on the T47D cell line. The cytotoxic effect of the SNEDDS of bay leaves was determined using an MTT assay, and the findings were read using an ELISA reader. Data analysis is calculated via linear regression methods by using Microsoft Excel software. The results showed that the SNEDDS of bay leaves performed cytotoxic effects on the T47D cell line with IC50 138 μg/mL. The results showed that the optimal composition formula SNEDDS, namely, Tween 20:PG:oleic acid = 2.25:2.25:0.5 in 5 mL SNEDDS preparation, which had a value of transmittance of 83.81% with emulsification time was less than 5 min; the average droplet size was 165.5 nm, and the zeta potential was −0.4 mV. The data analysis showed that the cytotoxicity effect of the SNEDDS of bay leaves is included in the moderate cytotoxic category.Keywords: Bay leaf, optimization, nanoemulsi, cytotoxicity