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All Journal Farmasains : Jurnal Farmasi dan Ilmu Kesehatan Jurnal Ilmiah Farmasi Statistika Jurnal Kedokteran Brawijaya Jurnal Teknosains Indonesian Journal of Cancer Chemoprevention Indonesian Journal of Pharmaceutical Science and Technology STOMATOGNATIC- Jurnal Kedokteran Gigi Indonesian Journal of Biotechnology Journal of Agromedicine and Medical Sciences Pharmacon Majalah Obat Tradisional Journal of Tropical Biodiversity and Biotechnology INDONESIAN JOURNAL OF PHARMACY JURNAL BIOLOGI INDONESIA Dental Journal (Majalah Kedokteran Gigi) The Indonesian Biomedical Journal Padjadjaran Journal of Dentistry Jurnal Kimia Terapan Indonesia JFIOnline YARSI Medical Journal Majalah Kesehatan Pharmamedika Pharmaceutical Sciences and Research (PSR)
Edy Meiyanto
Faculty Of Pharmacy, Universitas Gadjah Mada
Agriculture, Biological Sciences & Forestry Biochemistry, Genetics & Molecular Biology Chemical Engineering, Chemistry & Bioengineering Chemistry Civil Engineering, Building, Construction & Architecture Computer Science & IT Decision Sciences, Operations Research & Management Dentistry Economics, Econometrics & Finance Environmental Science Health Professions Immunology & microbiology Industrial & Manufacturing Engineering Materials Science & Nanotechnology Mathematics Mechanical Engineering Medicine & Pharmacology Public Health

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Journal : The Indonesian Biomedical Journal

 1 
GSH-conjugation Reduces PGV-1 Cytotoxicity and Its Ability in Downregulating N-Myc, β-catenin, and p62 Protein in Huh-6 Cells Utomo, Rohmad Yudi; Meiyanto, Edy; Susidarti, Ratna Asmah
The Indonesian Biomedical Journal Vol 17, No 4 (2025)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v17i4.3634

Abstract

BACKGROUND: Pentagamuvone-1 (PGV-1), a synthetic curcumin analogue, exhibits potent anticancer activity against Hepatocellular Carcinoma (HCC) by disrupting cell cycle regulation and downregulating key oncogenes such as N-Myc. Numerous studies have examined the role of glutathione (GSH) conjugation in modulating the anticancer properties of curcumin and its analogues. In contrast, the impact of PGV-1 metabolism, particularly GSH conjugation, and its implications for anticancer efficacy have not yet been elucidated. This study was performed to prepare GSH-conjugated PGV-1 (PGV-1-(GSH)2) as the model of PGV-1 metabolite and evaluate its potential distinct cytotoxicity on Huh-6 cells.METHODS: PGV-1 was synthesized via an acid-catalyzed reaction between 4-hydroxy-3,5-dimethylbenzaldehyde and cyclopentanone while PGV-1-(GSH)2 was obtained through reflux at 70oC for 2 hours. The cytotoxic effects of PGV-1 and PGV-1-(GSH)2 on Huh-6 and JHH4, two HCC cells, were assessed using a cell counting kit-8 (CCK-8) assay, while immunoblotting was performed to evaluate their impact on N-Myc and its downstream protein such as β-catenin, and p62.RESULTS: PGV-1-(GSH)2 was prepared through GSH conjugation of PGV-1 in orange color solution, as confirmed by Electrospray Ionization Mass Spectrometry (ESI-MS), Fourier Transform Infrared Spectroscopy (FT-IR), and Nuclear Magnetic Resonance (NMR) analysis. Cytotoxicity assays revealed that PGV-1-(GSH)2 exhibited less potent anticancer activity against HCC cells than PGV-1. GSH conjugation also decreased the ability of PGV-1 in downregulating the N-Myc, β-catenin, and p62 protein level.CONCLUSION: The prepared PGV-1-(GSH)2 reduces the cytotoxicity of PGV-1 and its ability on downregulating N-Myc, β-catenin, and p62 in Huh-6 cells. These findings highlight the need for further exploration about the study of PGV-1 metabolism which could affect the anticancer efficacy against HCC.KEYWORDS: curcumin, PGV-1, GSH, HCC, N-Myc
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
Co-Authors . Anindyajati . Larasati . Sugiyanto Adam Hermawan Adam Hermawan Adisusilo, Midori Rahmadhany Putri Aditya Fitriasari Aditya Fitriasari Agung Endro Nugroho Agusta Fauzi, Ilham Agustina Setiawati Ainun Wulandari Alexxander, . Alexxander, . Ameilinda Monikawati Ameilinda Monikawati Andita Pra Darma Andita Pra Darma Andriyani, Rina Angelina, Marissa Angraini, Sonia Meta Anif Nur Artanti, Anif Nur Ardriyanto, Maria Indra Arief Nurrochmad Arief Rahman Hakim Asih Triastuti Astrid Ayu Maruti Aulia Katarina Aulia Rahman, Faaza Ayu Maruti, Astrid B. Sudarto Banun Kusumawardani Chio Oka, Chio D., Andita Pra D., Andita Pra Da'i, Muhammad Da’i, Muhammad Dewi Arum Sekti, Dewi Arum Dewi Pamungkas Putri, Dyaningtyas Dewi Pratiwi Dini Maharani Djaswadi Dasuki Dwi Ana Nawangsari Dwi Ana Nawangsari, Dwi Ana Dwi Merry Christmarini Robin Dwi Nurahmanto Dyaningtyas D. P. Putri Dyaningtyas Dewi Putri Pamungkas Effendi, Fatiha Citra Endah Puji Septisetyani, Endah Puji Endah Puspitasari Endang Lukitaningsih Endang Purwaningsih Erlina Rivanti Erna Prawita Setyowati Esti, Yuni Fajar Fany Mutia Cahyani Farmasyanti, Cendrawasih Andusyana Feby Handoko, Fransiscus Fikri Amalia Fina Aryani Goenadi Fina Aryani Goenadi, Fina Aryani Fitria Rahmi Fiveri, Anis Fiveri, Anis Fortunella Tjondro Handayani, Sri Handayani, Sri Hanifa, Mila Hapsari, Novia Permata Hargiani, Fransisca Xaveria Harsan, Hayfa Salsabila Hastuti, Hanaan Emilia Adi Hendra Kurniawan Maury Hendri Wasito Heni Susilowati Herwandhani Putri Herwandhani Putri Ibrahim Arifin Ida Ayu Putu Sri Widnyani Ika Nurzijah Ika Rahmawati Sutejo Ikawati, Muthi' Ilham Agusta Fauzi Ilham Agusta Fauzi Imono Argo Donatus, Imono Argo Indrasetiawan, Puguh Indri Kusharyanti Inna Armandani, Inna Inna Armandari Iwan Sahrial Hamid JAKA WIDADA Jauhari, Fahmi Ihsanuddin Jenie, Riris Istighfari Jenie, Riris Istighfari Juni Ekowati Kadarsih Soejono, Sri Kadarsih Soejono, Sri Kartika Dyah Palupi Kartika Dyah Palupi Kato, Jun-Ya Kawai, Taro Kholid Alfan Nur Kholid Alfan Nur Komang Alit Paramitasari Kuijpers-Jagtman, Anne Marie Kumara, Dennaya Laras Widawaty Putri Lestari, Dinda Luthfia Indriyani M, Kawaichi M, Kawaichi Mae Sri Hartati Wahyuningsih Maran, Gergorius Gena Marcellino Rudyanto Maria Dwi Supriyati Maria Dwi Supriyati, Maria Dwi Masashi Kawaichi Masashi Kawaichi, Masashi Muflikhasari, Haruma Anggraini Muhammad Da'i Muhammad Fithrul Mubarok, Muhammad Fithrul Muthi Ikawati N., Perdana Adhi N., Perdana Adhi Nabila, Klarissa Nanda Resa Pratama Niken Nur W, Niken Novi Hastuti, Novi Novianti, Metta Novitasari, Dhania Nugraheni, Nadzifa Nunuk Aries Nurulita Nunuk Purwanti Nurma Sabila Nurrachma, Marsya Yonna P.K.W., Diah Ayu P.K.W., Diah Ayu Perdana Adhi Nugroho Perdana Adhi Nugroho Prasetyaningrum, Pekik Wiji Pudjono Pudjono Putri, Amaliya Permata Putri, Herwandhani Putri, Nindya Budiana R A Susidarti Raditya Prima Istiaji Rahmah, Inggita Hasi Rahman, Faaza Aulia Rahmawati, Desty Restia Rahmi Khamsita Ramadani, Ratna Dwi Ratih Hardika Pratama Ratna Asmah Susidarti Ratna Asmah Susidarti Retno Ardhani Retno Murwanti Rifai, Fauziah Novita Putri Riris I Jenie Riris I Jenie, Riris I Riris Istighfari Jenie Riris Istighfari Jenie Riris Istighfari Jenie Risdian, Chandra Rita Riata Rohmad Yudi Utomo Rohmad Yudi Utomo Rosa Adelina Rosana Anna Ashari Rosana Anna Ashari, Rosana Anna Rosye H.R. Tanjung Rul Afiyah Syarif Rumiyati, Rumiyati Salsabila, Irfani Aura Santoso, Christopher Filando Sari Haryanti Sari Haryanti Sarmoko Sarmoko Sendy Junedi Sendy Junedy, Sendy Shigeru Sasaki Sismindari . Sitarina Widyarini Sofa Farida Sri . Handayani Sri Handayani Sri Kadarsih Soejono Sri Kasianningsih Sri Susilowati Sri Tasminatun Sugeng Riyanto Sugiyanto . Sugiyanto . Sukardiman Supardjan A. M. Supardjan A.M., Supardjan Supardjan AM Supardjan AM, Supardjan Susi Ari Kristina Tutuk Budiati Udin, Zalinar Umar A. Jenie Umar Anggara Jenie Umar Anggara Jenie Umar Anggara Jenie Widayanti, Wasita Rachma Yundari, Yundari Yurista Gilang Yurista Gilang Ikhtiarsyah Yuyun Farida Yuyun Farida, Yuyun Zufairo, Shofa Khamdanatuz Zulfin, Ummi Maryam