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INDONESIA
Indonesian Journal of Cancer Chemoprevention
Published by Indonesian Society for Cancer Chemoprevention
ISSN : 23558989     EISSN : 20880197     DOI : -
Core Subject : Health, Science,
Biochemistry, Genetics & Molecular Biology Medicine & Pharmacology
Indonesian Journal of Cancer Chemoprevention (IJCC) is an open access, peer-reviewed, triannual journal devoted to publishing articles on Cancer Chemoprevention including Experimental and Clinical Pharmacology, especially concerning Anti-Oxidants, Anti-Aging, Anti-Inflammation, Anti-Angiogenesis, and Anti-Carcinogenesis; Cancer Detection; Stem Cell Biology; Immunology; in vitro and in silico Exploration of Chemopreventive Mechanism; and Natural Products.
Arjuna Subject : -
Articles 334 Documents
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Protein-protein Docking Studies of Estrogen Receptor Alpha and TRIM56 Interaction for Breast Cancer Drug Screening Binar Asrining Dhiani; Nunuk Aries Nurulita; Fitriyani Fitriyani
Indonesian Journal of Cancer Chemoprevention Vol 13, No 1 (2022)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14499/indonesianjcanchemoprev13iss1pp46-54

Abstract

Breast 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.
Revealing the Potential of Compounds in Sappan Wood as Cervical Cancer Metastasis Chemopreventive Agent With MMP9 Target Hanaan Emilia Adi Hastuti; Midori Rahmadhany Putri Adisusilo; Yusufia Asmarani Ashar; Edy Meiyanto; Riris Istighfari Jenie
Indonesian Journal of Cancer Chemoprevention Vol 13, No 1 (2022)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14499/indonesianjcanchemoprev13iss1pp22-32

Abstract

Matrix metalloproteinase-9 (MMP9) has an essential role in cervical cancer metastasis. Sappan wood extract (SWE) from Caesalpinia sappan contains metabolites that have pharmacological effects and can potentially inhibit metastasis by targeting the protein markers. This research aims to discover the potency of compounds in C. sappan as chemopreventive agents for metastasis in cervical cancer by targeting MMP9. SWE was obtained by maceration with methanol and analyzed using thin layer chromatography (TLC). In vitro cytotoxicity test of SWE on HeLa cells was performed by direct counting method. MMP9 expression profiles and survival rates in cervical cancer patients were explored through bioinformatics studies by the GEPIA database. The CMAUP and PubChem databases were used to obtain the metabolomic profile of SWE. SWE compounds’ activities on target proteins were obtained through KNIME software, while its interaction with MMP9 was analyzed using molecular docking with MOE software. We obtained SWE with a yield of 9.7% w/w. The extract contains brazilin and is indicated by the spot appearance at Rf 0.375. The cytotoxicity of SWE against HeLa cells was considered potential as the IC50 value was 54.93 μg/mL. Based on the bioinformatics analysis, there is a significant difference in MMP9 expression between normal and cervical cancer tissue. The patient’s survival probability decreased if MMP9 was overexpressed. The molecular docking results showed that active compounds of SWE bind to the MMP9 inhibition site with higher affinity compared to the native ligand. This study reveals that SWE potential to be developed as a chemopreventive agent through metastasis inhibition in cervical cancer by targeting MMP9.Keywords: Caesalpinia sappan L., metastasis, bioinformatics, molecular docking, MOE.
The Effectiveness of Topical 5-fluorouracil Treatment on Mouse Skin Squamous Cell Precancerous Lesions through Caspase-3 Expression Siti Nurkasanah; Aida S.D. Hoemardani; Evlina Suzanna Sinuraya; Puspita Eka Wuyung
Indonesian Journal of Cancer Chemoprevention Vol 13, No 1 (2022)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14499/indonesianjcanchemoprev13iss1pp12-21

Abstract

Skin 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 (p<0.05) and immunohistochemical analysis showed caspase-3 expression on 5-FU treatments (1%, 2%, and 5%) was not significantly different from the imiquimod treatment (p>0.05). 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.
Dietary Curcuma, a Powerful Epigenome Modulator in Breast Cancer: an In Silico Study Amel Elbasyouni; Leila Saadi; AbdelKarim Baha
Indonesian Journal of Cancer Chemoprevention Vol 13, No 1 (2022)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14499/indonesianjcanchemoprev13iss1pp61-70

Abstract

The inhibition of DNA methyltransferase-1 enzyme can strongly decrease the capacity of cells to enhance the tumour-genesis process. Members of the Estrogen-Related Receptors family regulate several elements of cellular metabolism. These are orphan nuclear receptors that regulate a wide range of functional gene networks involved in breast carcinogenesis and the regulation of associated methionine and folate cycles, providing a proven direct relationship to DNA methylation as a result. Moreover, dietary phytochemicals, such as Curcumin, can involve epigenetic modification, which may decrease the development of many types of cancer, especially breast cancer in women. We conducted this study to investigate the effect of Curcuma (PubChem ID: 969516) on the epigenetic modification and inhibition of the DNA methyltransferase-1 (PDB ID: 3PTA) activity and Estrogen-Related Receptors (PDB ID: 1XB7) using Molecular docking approach and computational tools that may inform whether the Curcuma could provide this protective anticancer effect or not. Interestingly, the DNA methyltrasferase1-Curcumin and Estrogen-Related Receptors-Curcumin complexes display a docking score of -6.9 and -7.1 kcal/mol, respectively. Furthermore, Curcumin displays hydrogen, Pi-Cation, Pi-Anion and Van der Waals bonds with active site residues of the targeted molecules. By targeting DNA methylation via the combined inhibition of estrogen-related receptors and DNMT1, our research opens up a new therapeutic path for breast cancer treatment.Keywords: curcumin, breast cancer, epigenetic, molecular docking, treatment.
Antiproliferative activity of Ethanolic Extract of Kembang Bulan (Tithonia diversifolia) Leaf on HeLa Cervical Cancer Cell Line Endah Puspitasari; Nuri Nuri; Indah Yulia Ningsih; Bawon Triatmoko; Dewi Dianasari
Indonesian Journal of Cancer Chemoprevention Vol 13, No 1 (2022)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14499/indonesianjcanchemoprev13iss1pp55-60

Abstract

Tithonia diversifolia has been showed to be cytotoxic and antiproliferative on colon cancer, glioblastoma, hepatoma, kidney cancer, breast cancer, lung cancer, melanoma, leukemia, ovary cancer, prostate cancer, and stomach cancer cell lines, but not on cervical cancer cells yet. Our research aimed to determine the cytotoxicity and antiproliferative activity of T.diversifolia leaf ethanolic extract on HeLa cervical cancer cell line. The cytotoxicity and the antiproferative activity assay were done using MTT method for 24 h for cytotoxic assay; and series of 24, 48, and 72 h for antiproliferative assay. The cytotoxic activity was analyzed using IC50, while the antiproliferative assay was analyzed based on the proliferation kinetics. All assays were done in triplicate. T.diversifolia leaf ethanolic extract exhibited strong cytotoxic activity on HeLa cervical cancer cell lines with the IC50 of 97.839±10.120 μg/mL. The cytotoxic activity was dose dependent. Based on the proliferation assay, the antiproliferative activity was stronger as the incubation time and the dose increases. T.diversifolia leaf ethanolic extract showed strong cytotoxic and antiproliferative activity on HeLa cervical cancer cell lines.Keywords: T.diversifolia leaf ethanolic extract, cytotoxicity assay, antiproliferative assay, HeLa cervical cancer cells.
In Silico Study of Chemical Compounds in Plantago major L. as Anti-Androgen Achmad Al Baihaqi; Hasna Siti Munifah Isman; Ganis Fitria Fauziyyah; Rismauli Ruth Natasari Hutabarat; Adi Hartono; Sandra Megantara
Indonesian Journal of Cancer Chemoprevention Vol 13, No 1 (2022)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14499/indonesianjcanchemoprev13iss1pp33-45

Abstract

Prostate cancer is the most common type of cancer diagnosed in men worldwide and the second leading cause of death after lung cancer. Testosterone and dihydrotestosterone (DHT) have been known to play an essential role in prostate cancer. Androgen receptor (AR) binding to the ligand allows homodimerization and translocation to the nucleus, which acts as a transcription factor for androgen-responsive genes such as PSA (Prostate-specific antigen). Although many anti-androgens have been established, including Bicalutamide, Flutamide, and Abiraterone, the problem of non-specific cytotoxicity effects and cancer recurrence due to potential drug resistance remains a significant obstacle to establishing effective therapy. Plantago major L. is one of the plants that can choose anticancer therapy because, based on reports, it has anticancer activity through DNA damage in cancer cells. This study focused on the search for the potential phytochemical activity of Plantago major L. as an anti-androgen, non-cytotoxic, and had significant AR inhibitory activity. This study uses Lipinski prediction (RO5), ADMET prediction, and a structure-based approach with molecular docking techniques using the PDB ID 2AM9 receptor structure and 13 compounds from Plantago major L. as test ligands compared to known AR antagonists. From the research results, Hispidulin has the highest potential as an anti-androgen with binding energy (-9.43 kcal/mol) that is closest to natural ligands and is smaller than Flutamide as a comparison drug. This anti-androgen activity was hypothesized from the similarity of hydrogen bonds with amino acid residues 705-Asn and 711-Gln as key AR residues present in Hispidulin.Keywords: Prostate cancer, Androgen Receptor, Plantago major L., ADMET, In Silico.
Antimigratory Evaluation from Curcumin-Derived Synthetic Compounds PGV-1 and CCA-1.1 on HCC1954 and MDA-MB-231 Cells Dhania Novitasari; Edy Meiyanto; Jun-ya Kato; Riris Istighfari Jenie
Indonesian Journal of Cancer Chemoprevention Vol 13, No 2 (2022)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14499/indonesianjcanchemoprev13iss2pp71-82

Abstract

Earlier 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.
Electric Field-Based Cancer Therapy Induces the Expression of HMGB1 and PD-L1 mRNA Genes on Breast Tumor of Female Rats Siti Fathurrohmah; G.A.B Yehezkiel P. Cahyadi; Firman Alamsyah; Rarastoeti Pratiwi
Indonesian Journal of Cancer Chemoprevention Vol 13, No 2 (2022)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14499/indonesianjcanchemoprev13iss2pp128-136

Abstract

Electro Capacitive Cancer Therapy (ECCT) is an electric field-based cancer therapy method using intermediate frequency (150 kHz) and low intensity (18 Vpp). High Mobility Group Box 1 (HMGB1) is a cytokine related to damage-associated molecular patterns (DAMPs) secreted by dead cells. The expression of Programmed Death Ligand 1 (PD-L1) is ligand present on the surface of tumor cells and its expression is associated with the increase in the number CD8+ T lymphocytes. This study aims to examine the effect of ECCT exposure on the expression of HMGB1 and PD-L1 genes on the breast tumor, brain, and liver tissues of Rattus norvegicus (Berkenhout, 1769). The tissues were obtained from the previous studies stored in RNAlater (-20˚C). Female rat tissues of the previous study from four treatment groups, namely the control group (NINT), non-DMBA-induction with therapy (NIT), DMBA-induction with non-therapy (INT), and DMBA-induction with therapy (IT). Gene expression was analyzed using the RT-qPCR. Statistical t-test with a p<0.05 significance level was performed using GraphPad Prism 9.4.0 software. The result shows HMGB1 and PD-L1 mRNA genes were both significantly expressed in breast tumor samples. The liver and brain samples of normal rats did not show any significant changes in the activity of these genes after exposure to the electric field. This study indicates that exposure to electric fields may trigger the expression of HMGB1 and PD-L on the rat’s breast tumor samples. This study also provides information related to the safety of ECCT in healthy organs of female rats, especially the brain and liver.Keywords: ECCT, breast tumor, HMGB1, PD-L1, IFN- γ.
In Silico Study of Compounds in Bawang Dayak (Eleutherine palmifolia (L) Merr.) Bulbs on Alpha Estrogen Receptors Sunani Sunani; Maya Andani; Asilla Mauri Ramdini Kamaludin; Nyai Ayu Sylfia Stannia Puspitasari Helmi; Kaila Keyshia Mei; Yunitasya Guspira; Oktavia Sabetta; Diah Lia Aulifa
Indonesian Journal of Cancer Chemoprevention Vol 13, No 2 (2022)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14499/indonesianjcanchemoprev13iss2pp83-93

Abstract

Breast cancer is an uncontrolled malignancy of the breast that originates from glandular cells, gland ducts, and the supporting tissues of the breast. The development of herbal-based anticancer drugs is progressing, one of which is derived from the natural ingredients of Eleutherine palmifolia tubers. The aim of this study was to determine the activity of compounds derived from Eleutherine palmifolia tubers on the alpha-estrogen receptor (ERα) using an in silico study. The crystal structure of the enzyme used was 3ERT which was obtained from the Protein Data Bank (PDB). The applications used in this journal are Chem3D (initial preparation of ligands and receptors), AutoDock4 (redocking and calculation of root mean square deviation (RSMD)), and Biovia (visualization of redocking results). Tamoxifen was used as a reference ligand. Based on the results of the in silico study, the best compound that has the potential to be developed as a candidate for anticancer drug is Eleutherine because the results of the in silico test on Eleutherine have a value of G=-7.56 kkal/mol and the smallest KI=2.89 nM, so it can be concluded that eleutherine is one of potential drug candidate for anti cancer.Keywords: Breast cancer, eleutherine, estrogen receptor α.
Clinical Profile and Treatment Outcome of Chordoma: A Tertiary Care Experience in North India Tavseef Ahmad Tali; Fiza Amin; Javaid Ahmad Dar; Mushtaq Ahmad Sofi; Nazir Ahmad Dar
Indonesian Journal of Cancer Chemoprevention Vol 13, No 2 (2022)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14499/indonesianjcanchemoprev13iss2pp137-143

Abstract

Chordoma 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.

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