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All Journal Indonesian Journal of Cancer Chemoprevention Indonesian Journal of Biotechnology The Indonesian Biomedical Journal
Rohmad Yudi Utomo
Cancer Chemoprevention Research Center Faculty Of Pharmacy Universitas Gadjah Mada
Biochemistry, Genetics & Molecular Biology Immunology & microbiology Materials Science & Nanotechnology Medicine & Pharmacology Public Health

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Diosmin Enhances the Anti-migration Activity of Curcumin Analog PGV-1 on Colorectal Cancer Cells Ikawati, Muthi; Utomo, Rohmad Yudi; Hapsari, Novia Permata; Meiyanto, Edy; Oka, Chio
The Indonesian Biomedical Journal Vol 16, No 1 (2024)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v16i1.2829

Abstract

BACKGROUND: Diosmin enhances the cytotoxicity of Pentagamavunone-1 (PGV-1) in cancer cells. PGV-1 and diosmin are predicted to target several matrix metalloproteinases (MMPs) in metastatic cancer, including colorectal cancer, but the anti-migration potency of their combination has not established yet. This study evaluates the anti-migration effect of PGV-1 and diosmin combination in colorectal cancer.METHODS: The cytotoxicity assay using Cell Counting Kit 8 (CCK-8) method in WiDr colorectal cancer cells was carried out to determine the concentration for anti-migration experiments. The wound healing assay was used to observe the anti-migration activity by measuring the cell-free area. Gelatin zymography was employed to detect the MMP activity indicating by the clear band density. The interaction between PGV-1 or diosmin and MMP proteins was predicted by molecular dockings.RESULTS: PGV-1 was cytotoxic (IC50 17 mM), while diosmin up to 100 mM did not affect cell viability. Both 10 mM PGV-1 as well as 50 and 100 mM diosmin slowed down the closure of cell-free area. A 100 mM diosmin was significantly enhance the anti-migratory activity of 50 and 100 mM PGV-1. The activity of MMP-9 and MMP-2 was also lower in the presence of diosmin compared to than that of PGV-1 alone. PGV-1 or diosmin was also able to interact with MMP proteins with a lower energy compared to than that of the native ligands.CONCLUSION: Diosmin enhances the anti-migration activity of PGV-1 in WiDr cells, possibly by affecting MMPs’ activity. This study is an evidence that diosmin is a potential co-chemotherapy candidate for PGV-1, that can be utilized to overcome metastatis in colorectal cancer.KEYWORDS: cancer, citrus flavonoid, co-chemotherapy, diosmin, matrix metalloproteinases (MMPs), migration, Pentagamavunone-1, WiDr cancer cell
The Chemopreventive Potential of Diosmin and Hesperidin for COVID-19 and Its Comorbid Diseases Utomo, Rohmad Yudi; Ikawati, Muthi'; Putri, Dyaningtyas Dewi Pamungkas; Salsabila, Irfani Aura; Meiyanto, Edy
Indonesian Journal of Cancer Chemoprevention Vol 11, No 3 (2020)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14499/indonesianjcanchemoprev11iss3pp154-167

Abstract

The COVID-19 becomes worse with the existence of comorbid diseases such as cardiovascular diseases, metabolic syndromes, inflammation, degenerative diseases, as well as cancer. Therefore, a comprehension approach is needed to combat such comorbid conditions, not only focusing on the virus infection and replication but also directed to prevent the raising comorbid symptoms. This study analyzed the potential natural compounds, especially diosmin and hesperidin, as an anti-SARS-CoV-2 and chemopreventive agent against several COVID-19 comorbid diseases by using an in-silico method. Diosmin and hesperidin together with other natural compounds and existing viral drugs (lopinavir, nafamostat, and comastat) were docked into several proteins involved in SARS-CoV-2 infection and replication namely SARS-CoV-2 protease (PDB:6LU7), spike glycoprotein-RBD (PDB:6LXT), TMPRSS2, and PD-ACE2 (PDB:6VW1) using MOE software. The interaction properties were determined under docking score values. The result exhibited that diosmin and hesperidin performed superior interaction with all the four proteins compared to the other compounds, including the existing drugs. Moreover, under literature study, diosmin and hesperidin also elicit good chemopreventive properties against cardiovascular disorder, lung and kidney degeneration, as well as cancer development. In conclusion, diosmin and hesperidin possess high opportunity to be used for the COVID-19 and its the comorbid diseases as chemopreventive agents.Keywords: chemoprevention, COVID-19, diosmin, hesperidin, SARS-CoV-2 infection
Network Pharmacology and In Vitro Validation of Brazilin as a Potential Apoptosis-Inducing Agent in HBV-Related Hepatocellular Carcinoma Hanifa, Mila; Utomo, Rohmad Yudi; Jenie, Riris Istighfari
Indonesian Journal of Cancer Chemoprevention Vol 15, No 3 (2024)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14499/indonesianjcanchemoprev15iss3pp210-223

Abstract

Hepatitis B virus (HBV) reactivation-related hepatocellular carcinoma (HCC) presents a significant threat due to its potential to cause liver failure and mortality. Consequently, the discovery of novel treatments that offer anticancer efficacy and liver protection is urgently needed. Brazilin, a natural compound, has previously been reported to possess cytotoxic and liver-protective properties. This research aimed to investigate the potency of brazilin in suppressing the growth of HCC cells through in silico and in vitro approaches. Hep3B cells, which harbor integrated HBV DNA, were selected as the HCC model, with PGV- 1 utilized as a positive control. The in silico study used network pharmacology to predict brazilin’s potential gene targets. Cytotoxicity was evaluated using the CCK-8 assay, and apoptosis detection was carried out using Annexin V/PI staining followed by flow cytometry. The analysis predicted that brazilin targets key genes such as SRC, EGFR, AKT1, GRB2, IGF1, ESR1, STAT1, MMP9, JAK2, and PPARG involved in cancer proliferation and metastasis. Proteins such as SRC, GRB2, and MMP9 are overexpressed in TP53-mutated HCC and linked to low survival. Brazilin showed moderate cytotoxicity with an IC50 value of 17 μM at 72 h and significantly induced apoptosis in Hep3B cells. These findings suggest that brazilin is a promising apoptosis-inducing agent for HBV-related HCC.Keywords: brazilin, Hep3B cell lines, network pharmacology, cytotoxic, apoptosis.
Pentagamaboronon-0-Sorbitol Induces Apoptosis through Elevation of Reactive Oxygen Species in Triple Negative Breast Cancer Cells Ramadani, Ratna Dwi; Utomo, Rohmad Yudi; Hermawan, Adam; Meiyanto, Edy
Indonesian Journal of Cancer Chemoprevention Vol 12, No 1 (2021)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14499/indonesianjcanchemoprev12iss1pp46-56

Abstract

Breast cancer is the most common type of cancer causing mortality for women due to metastasis. More than 50% of breast cancer patients are suffered lung metastases. One strategy to target the cancerous cell is Boron Neutron Captured Therapy (BNCT) which showed high affinity toward cancer cells and reported to have anti-proliferative as well as anti-metastatic activities. Pentagamaboronon-0 (PGB-0) is a curcumin analogue substance which had reported to exert anticancer activities against Her-2 expressing as well as triple negative breast cancer cells. Despite its great potency as BNCT agent candidate, this compound also exerted several anticancer properties. Complex formation of this substance with sorbitol was achieved to improve the solubility and maximize compound’s delivery to the target cells. This study aimed to investigate the ability of Pentagamaboronon-0-Sorbitol (PGB-0-So) to modulate cell cycle and induce apoptosis especially through the mechanisms of reactive oxygen species (ROS) modulation. The 3-(4,5-dimethylthiazzol-2yl)-2,5-diphenyltetrazolium (MTT) cytotoxicity assay of PGB-0-So against 4T1 breast cancer cell line were found to exert potential effect in dose-dependent manner with lethal concentration (IC50) values of 39 μM. The cytotoxicity of PGB-0-So complex was found to be increased considerably compared with that of PGB-0. Cell cycle modulation identified using propidium iodide (PI) staining showed cell accumulation in S phase following treatment with PGB-0-So. Apoptosis induction assay analyzed using flowcytometer with Annexin V and PI staining on its IC50 dose was found to induce programmed cell death (apoptosis). The sub-IC50 treatment of this compound was also improved the cellular ROS level which also took role in apoptosis induction. These findings suggest that PGB-0-So is potential as an anticancer agent.Keywords: Curcumin analogue, PGB-0-So, Anticancer, 4T1 cell line, ROS modulation.
Co-Authors Adam Hermawan Annisa Novarina Bani Adlina Shabrina Chio Oka, Chio Dyaningtyas Dewi Putri Pamungkas Edy Meiyanto Edy Meiyanto Edy Meiyanto Edy Meiyanto Edy Meiyanto Edy Meiyanto Hanifa, Mila Hapsari, Novia Permata Ikawati, Muthi' Indah Hairunisa Jenie, Riris Istighfari Juang Juansa Lailatul Qodria Lailatul Qodria Marvin Lambertus Marvin Lambertus Muthi Ikawati Nindya Budiana Putri Prisnu Tirtanirmala Rahmi Khamsita Rahmi Khamsita Raisatun Nisa Sugiyanto Raisatun Nisa Sugiyanto Ramadani, Ratna Dwi Ratna Asmah Susidarti Ratna Asmah Susidarti Ratna Dwi Ramadani Retno Murwanti Riris Istighfari Jenie Riris Istighfari Jenie Riris Istighfari Jenie Salsabila, Irfani Aura Yogi Ertanto Yogi Ertanto