Indonesian Journal of Cancer Chemoprevention
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Analysis of SARS-CoV-2 spike-Induced Syncytia with Lifeact-GFP as Biosensor Using High-Content Screening Instrument for Automated Syncytia Counting
Full text linkSARS-CoV-2 is believed to cause cytopathic effects in forming multinucleated cells, known as syncytia. Syncytia due to SARS-CoV-2 infection found in lung tissue samples of COVID-19 patients represents a case of COVID-19 with a poor prognosis. Therefore, it is very important to study the mechanism of syncytia formation and to test candidate materials that can inhibit the occurrence of syncytia and potentially be applied in the treatment or prevention of COVID-19. Since syncytia counting and analysis are time-consuming, we utilized a high-content screening (HCS) instrument in this study to automate syncytia analysis. We used 293T cells transfected with plasmids to express the SARS-CoV-2 spike, human angiotensin-converting enzyme-2 (hACE-2), and a plasmid encoding lifeact-GFP as an F-actin biosensor to facilitate syncytia analysis using the HCS instrument. In this study, syncytia analysis was carried out using HCS software. The HCS application categorizes cells as multi-nuclei by counting the number of cell nuclei stained with DAPI in cells that emitted green fluorescence due to lifeact-GFP expression. Syncytia analysis is time-consuming because of the calculation of the number of syncytia formed in a confluent cell monolayer culture. Hopefully, utilizing the HCS platform can accelerate the test of syncytia inhibition after various treatments using test compounds.Keywords: 293T cells, high-content analysis, SARS-CoV-2, spike, syncytia
Evaluation of the Potential In Vitro effects of Plantago major L. on Wound Healing in Human Umbilical Vein Endothelial Cells (HUVEC)
Full text link The treatment of skin wounds remains a major concern in the field of medicine, particularly in the case of chronic wounds resulting from various disorders such as diabetes. The utilization of herbs or herbal preparations for the purpose of healing skin wounds presents a therapeutic challenge within the realm of traditional medicine. Plantago major L. is known to have bioactive compounds that have wound healing activity such as aucubin. This study aimed to determine the in vitro wound healing potential of Plantago major L. extract (PLE). The study involved several assays, including phytochemical examination of PLE using TLC, cell viability testing using MTT assay, and wound healing testing using scratch assay on human umbilical vein endothelial cells (HUVEC). The results confirmed the presence of aucubin as one of the compounds in PLE. It was observed that PLE with 125 μg/mL exhibited the highest wound closure percentage at 90.66%. This study shows that PLE possesses wound healing capabilities.Keywords: Plantago major L., PLE, cytotoxic assay, wound scratch assay, HUVEC
In Vitro Anti-Photoaging Properties of Phylanthus urinaria L. Herb Extract
Full text linkThe overexposure to ultraviolet (UV) radiation from sunlight is related to photoaging of the skin and high risk of skin cancer. Sunscreen material and antioxidants are commonly used to protect skin from harmful UV. However, the application of synthetic compounds in sunscreen products is regulated to a limited amount because it can produce photosensitizers, inducing adverse reactions in the skin, and also harmful to the environment. Ethanol extract of Phyllanthus urinaria L. herb possesses a strong antioxidant activity similar to ascorbic acid, which makes it potential to substitute the synthetic compound in sunscreen products. Therefore, this research was conducted on the 70% ethanol extract of P. urinaria herb to analyze its in vitro anti-photoaging properties, i.e., antioxidant, protein antiglycation and antiinflammation, also to determine the Sun Protection Factor (SPF) and the quantitative composition of the metabolites. The extract exhibited a strong antioxidant activity IC50 of 3.01 mg/L, a higher moderate antiglycation activity IC50 of 216.67 mg/L, but low anti-inflammatory activity IC50 of 86.61mg/L. The presence of saponin, phenolic compounds, flavonoids, tannins, and methyl linoleates is suggested to contribute to the anti-photoaging properties. According to the anti-inflammatory assay, the extract may not inhibit signaling pathways that follow cytokine expression but possibly inhibit those that precede cytokine expression due to its antioxidant activity. An SPF value of 5.95 at 50 mg/L meets the recommended range for the skin phototypes of Southeast Asian, dark-skinned Asian, and African people. These results indicate that P. urinaria extract has potential as an anti-photoaging material for sunscreen products.Keywords: antiglycation, antiinflammation, antioxidation, Phyllanthus urinaria L., SPF
The Study of Molecular Docking and Molecular Dynamics Simulation Chemical Compound of Pycnarrhena cauliflora Diels. as Proapoptosis in Cervical Cancer
Full text linkCervical cancer is one of the most common cancers among women worldwide and in Indonesia. B-cell lymphoma 2 (Bcl-2) can play a role in causing cancer by inhibiting apoptosis. The purpose of this study was to analyze the chemical compound of the sengkubak plant (Pycnarrhena cauliflora Diels.), which can act as antiapoptotic inhibitor by binding to the B-cell lymphoma 2 (Bcl-2) receptor. The research was conducted in silico with molecular docking methods and molecular dynamics simulations. Molecular docking used the AutoDock 4.2.6 software and visualization used Biovia Discovery Studio. Molecular dynamics simulation used Gromacs 5.1.2 software and result visualization used Grace. Longipinocarvone was the best test ligand with the smallest ΔGbind value of -6.99 kcal/mol compared to the positive control of Doxorubicin and other compounds which indicating Longipinocarvone’s affinity for binding to the Bcl-2 receptor was better than Doxorubicin. The types of interactions involved in the molecular docking of the chemical compounds of the sengkubak plant and Doxorubicin including hydrogen bonds and hydrophobic interactions. The stability of the bond between the ligand protein complex resulting from molecular docking was analyzed based on the parameters RMSD, RMSF, Radius of Gyration (Rg) values through molecular dynamics simulations. The results of the analysis showed that Longipinocarvone and Doxorubicin had a stable bond with Bcl-2 as indicated by the RMSD and RMSF values meeting the requirements, namely <3 Å (0.3 nm). The Rg graph showed both complexes are stable during simulation and have resemblant ligand-protein movements.Keywords: Cervical cancer, B-cell lymphoma 2 (Bcl-2), Pycnarrhena cauliflora Diels., molecular docking, molecular dynamics
Cytotoxic Effects of Cinnamon Powder and Lemongrass Oil-Enriched Roselle Tea on T47D Breast Cancer Cells
Full text linkBreast cancer is the most prevalent cancer among women and is the leading cause of cancer-related mortality worldwide. This underlines the importance of preventive strategies to reduce the risk. Harnessing natural products like tea could be an alternative preventive strategy. In this study, the chemopreventive potential of roselle flower tea (Hibiscus sabdariffa L.) enriched with cinnamon oil (Cinnamomum burmannii) and lemongrass (Cymbopogon citratus) was evaluated. The tea was formulated using a stirred boiler tank and tested for its cytotoxicity against T47D cells using the MTT method. The cytotoxicity test showed that with the addition of cinnamon oil and lemongrass, roselle tea had more significant cytotoxic activity against T47D cancer cells than pristine roselle tea. Adding 5 g of cinnamon and lemongrass oil vapor for 15 seconds into the tea showed the highest cytotoxicity, with an IC50 of 730 μg/mL. This value is almost three times higher than without adding cinnamon oil and lemongrass. In conclusion, adding cinnamon oil and lemongrass to the roselle tea formulation can increase cytotoxic activity against T47D cancer cells, indicating its potential as a natural anti-cancer agent.Keywords: Chemopreventive, Cinnamon, Lemongrass, Roselle Tea, T47D Cells
Molecular Insights into Breast Cancer Treatment: An Integrated Approach of Network Pharmacology and Component Analysis for Lansium parasiticum Bark Extract
Full text linkMedicinal plants containing multi-components have the potential for multi-target genes, multi-pathways, and various effects on diverse diseases. With the increasing technological advancements, understanding the complex interactions between multi-component substances and biological systems is becoming more crucial. In this context, conventional experimental research might have limitations as it typically focuses on the impact of one component on one gene. The objective of this research is to identify compounds in the bark extract of Lansium parasiticum and elucidate the molecular mechanisms of these compounds in inhibiting the progression of breast cancer cells using a network pharmacology approach. Compound identification in Lansium parasiticum bark extract (LPBE) has been conducted using Liquid Chromatography Tandem Mass Spectrophotometry (LC-MS/MS) technique. ADMET predictions were utilized to determine the absorption and bioavailability profiles. A network pharmacology approach employing Cytoscape 3.9.1, GeneCards, Disgenet, STRING 2.0.0, SRplot, and Kyoto Encyclopedia of Genes and Genomes (KEGG) was used to predict the anti-cancer molecular mechanisms of these compounds. Seventeen active compounds have been successfully identified via LC-MS/MS. Among these, the compounds Moronic Acid, 4-Morpholineacetic Acid, and Ursolic Aldehyde were found in the highest concentrations. The results of the network pharmacology analysis indicate that the compounds in LPBE are involved in three potential pathways for breast cancer treatment: the NF-κß signaling pathway (hsa 04064), microRNA in cancer (hsa05206), and apoptosis (hsa04210). Target genes implicated in these pathways include BAX, BCL2, TNF-α, PARP1, STAT3, NOTCH1, and NF-κß1. It can be concluded that LPBE contains compounds with potential for treating breast cancer, as they are predicted to interact with relevant target pathways and genes. Therefore, further research is highly recommended, particularly in the development of drugs for breast cancer.Keywords: apoptosis, microRNA, NF-κß, TNF-α, STAT3
Physicochemical Characterization, Cytotoxic Activity, and Caspase-9 Expression of Nanogold-Parijoto (Medinilla Speciosa Reinw .Ex, Bl ) in Hela Cell Lines
No full textParijoto (Medinilla speciosa, Reinw. ex. Bl.), a tropical plant native to Southeast Asia, contains flavonoids, tannins, and saponins, which have the potential as an anticancer. Gold nanoparticle-based drug formulations are applied to increase the anticancer effectiveness of herbal medicines. The compounds in the stalk of parijoto have the potential to be bioreductor in the biosynthesis of gold nanoparticles. This study aims to determine the physicochemical characterization, cytotoxic activity, and expression of protein caspase-9 after treatment with nanogold parijoto (AuNPs-PR) on HeLa cell. The nanogold biosynthesis process was done by reacting 1 mM HAuCl4 with parijoto aqueous extract (EP). Physicochemical characterization measure of particle size, Polydisperse Index (PdI), and zeta potential of AuNPs-PR was carried out using a particle size analyzer. The cytotoxic effect and viability cell of AuNPs- PR were carried out using the MTT assay. The expression of caspase-9 was observed by immunocytochemistry assay. Physicochemical characterization of AuNPs-PR shows that the particle size value is 160.8 nm with PdI and zeta potential values of 0.430 and -4.56 mV respectively. In the MTT assay, both AuNPs-PR and EP demonstrated a reduction in the viability of Hela cells after 24 h in a dose-dependent manner, yielding IC50 values of 3.28 μg/mL and 19.22 μg/mL, respectively. AuNPs-PR and EP showed low cytotoxic activity against Vero normal cells, with IC50 values of over 500 μM. Further, the immunocytochemistry assay indicated that there was upregulation of caspase-9 by their expression. These results indicate that AuNPs-PR could effectively induce apoptosis in HeLa cells by upregulating caspase-9.Keywords: caspase-9, HeLa cells, MTT, nanogold, parijoto
Neoadjuvant and Adjuvant Surgical Interventions in Oncology: Optimizing Treatment Pathways
Full text linkThe advancement of cancer treatment has seen significant progress through the integration of neoadjuvant and adjuvant therapies, particularly within the realm of surgical oncology. This literature review follows a systematic approach using PRISMA guidelines, analyzing studies from databases such as PubMed, Google Scholar, Scopus, and Web of Science. The review examines the historical progression, current practices, and future directions of multimodal approaches, focusing on the synergistic benefits of surgery, drug development, targeted therapies, and technological innovations. Neoadjuvant interventions, designed to shrink tumors preoperatively, enhance surgical outcomes by improving resectability, while adjuvant therapies, administered postoperatively, aim to eliminate residual disease and reduce recurrence risk. Findings from clinical trials and case studies highlight improved survival rates, increased tumor resectability, and enhanced patient outcomes through the combination of these therapies. Additionally, the review emphasizes the crucial role of personalized medicine, molecular profiling, and emerging surgical technologies in refining treatment pathways. As the landscape of cancer care evolves, optimizing treatment sequencing and tailoring therapies to individual tumor profiles will be essential for maximizing therapeutic efficacy and improving patient prognosis.Keywords: Neoadjuvant Therapy, Adjuvant Surgical Intervention, Surgical Oncology, Multimodal Cancer Treatment, Targeted Cancer Therapy
CAR-T Cell Therapy: Revolutionizing Cancer Treatment
Full text linkCAR-T cell therapy has emerged as a groundbreaking approach in cancer treatment, offering new hope for patients with refractory and relapsed malignancies. This literature review provides a comprehensive overview of the development, applications, and future directions of CAR-T cell therapy. We explore the principles behind CAR-T cell engineering, highlight the clinical successes and challenges in treating hematologic malignancies, and discuss the potential and hurdles in targeting solid tumors. The review also examines the safety profiles, including adverse effects management, and delves into the mechanisms of resistance and relapse. Furthermore, we address regulatory and ethical considerations, patient perspectives, and the innovative advancements shaping the future of CAR-T cell therapy. By synthesizing current research and clinical data, this review underscores the transformative impact of CAR-T cell therapy in oncology and its promising trajectory in the fight against cancer.Keywords: CAR-T cell therapy, cancer treatment, hematologic malignancies, solid tumors, next-generation CAR-T
Rosmarinic Acid from Orthosiphon aristatus Potentially Targets Estrogen Receptor-Alpha in Breast Cancer: In-silico Study
Full text linkBreast cancer is the most common cancer among women. Tamoxifen, a widely used estrogen receptor-alpha (ER-α) inhibitor, is effective but often causes side effects, necessitating the search for alternative inhibitors from natural sources. Ortosiphon aristatus, also known as cat's whiskers, is a medicinal plant traditionally valued for its anti-inflammatory and antioxidant properties. Recent studies suggest its bioactive compounds may exhibit anticancer activity by inducing apoptosis in cancer cell lines. This study explores the potential of O. aristatus metabolites as ER-α inhibitors using computational approaches. Nine metabolites were assessed for their physicochemical properties based on Lipinski’s rule of five and ADMET predictions, followed by pharmacophore-based virtual screening with LigandScout and molecular docking with AutoDock. The results showed that all tested compounds complied with Lipinski’s rule, and most met ADMET criteria. Among these, rosmarinic acid was identified as one of the hit compounds based on pharmacophore screening, exhibiting binding interactions comparable to 4-hydroxytamoxifen with the ER-α amino acid residues HIS524 and GLY521. It also demonstrated a binding energy of -8.02 kcal/mol and a low inhibition constant (Ki) of 1.31 μM. These findings highlight the potential of O. aristatus and rosmarinic acid for further evaluation as candidates against ER-α in breast cancer cells.Keywords: breast cancer, estrogen receptor-alpha, Orthosiphon aristatus, in silico