Identification of novel functional compounds from forest onion and its biological activities against breast cancer

The discovery of new molecules from natural sources for the treatment of tumors such as breast cancers is of importance for the development of functional foods and to the pharmaceutical industry. A natural resource with potential activity against breast cancer is forest onion, Eleutherine bulbosa (M...

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Main Authors: Fahrul Nurkolis, Isma Kurniatanty, Elvan Wiyarta, Happy Kurnia Permatasari, Nelly Mayulu, Nurpudji Astuti Taslim, Raymond Rubianto Tjandrawinata, Hardinsyah Hardinsyah, Trina Ekawati Tallei, Apollinaire Tsopmo, Son Radu, Edwin Hadinata, Bonglee Kim, Rosy Iara Maciel Azambuja Ribeiro, Rony Abdi Syahputra
Format: Article
Language:English
Published: Elsevier 2024-12-01
Series:Journal of Agriculture and Food Research
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2666154324003995
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author Fahrul Nurkolis
Isma Kurniatanty
Elvan Wiyarta
Happy Kurnia Permatasari
Nelly Mayulu
Nurpudji Astuti Taslim
Raymond Rubianto Tjandrawinata
Hardinsyah Hardinsyah
Trina Ekawati Tallei
Apollinaire Tsopmo
Son Radu
Edwin Hadinata
Bonglee Kim
Rosy Iara Maciel Azambuja Ribeiro
Rony Abdi Syahputra
author_facet Fahrul Nurkolis
Isma Kurniatanty
Elvan Wiyarta
Happy Kurnia Permatasari
Nelly Mayulu
Nurpudji Astuti Taslim
Raymond Rubianto Tjandrawinata
Hardinsyah Hardinsyah
Trina Ekawati Tallei
Apollinaire Tsopmo
Son Radu
Edwin Hadinata
Bonglee Kim
Rosy Iara Maciel Azambuja Ribeiro
Rony Abdi Syahputra
author_sort Fahrul Nurkolis
collection DOAJ
description The discovery of new molecules from natural sources for the treatment of tumors such as breast cancers is of importance for the development of functional foods and to the pharmaceutical industry. A natural resource with potential activity against breast cancer is forest onion, Eleutherine bulbosa (Mill.) Urb., but the identity of its active constituents and their mechanisms of action remain unexplored. Therefore, this study focuses on metabolite profiling, in silico or pharmacoinformatic activity and mechanisms, as well as advanced validation on in vitro cell lines. Ten compounds identified in E. bulbosa bulb ethanolic extract (EBE) showed cancer receptor and radical inhibitory activity via network pharmacology and molecular docking simulation. The most promising compound was avenasterol binding PARP-1, HER2, iNOS receptors with values of −11.26, −8.34, and −9.17 μg/mL, respectively. EBE and avenasterol had a smaller EC50 value, or higher potency, than the control antioxidant Trolox in radical scavenging tests with ABTS and DPPH. In line with the in silico study, EBE and avenasterol showed antiproliferative activity against human breast cancer MCF-7 with LD50 217.8 μg/mL, with relatively low cytotoxicity to normal MCF-10A cells (LD50 > 1000 μg/mL). The antiproliferative mechanism of EBE on MCF-7 was associated with downregulation of TGF-β, HER2, PI3K, and AKT which are known tumor activators. Significant (p < 0.05) upregulation of tumor suppressor gene miR-29a-3p in MCF-7 was observed after treatment with EBE in a dose-dependent manner.
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spelling doaj-art-84182acedf474881a495c067e542b5ad2025-08-20T01:56:41ZengElsevierJournal of Agriculture and Food Research2666-15432024-12-011810136210.1016/j.jafr.2024.101362Identification of novel functional compounds from forest onion and its biological activities against breast cancerFahrul Nurkolis0Isma Kurniatanty1Elvan Wiyarta2Happy Kurnia Permatasari3Nelly Mayulu4Nurpudji Astuti Taslim5Raymond Rubianto Tjandrawinata6Hardinsyah Hardinsyah7Trina Ekawati Tallei8Apollinaire Tsopmo9Son Radu10Edwin Hadinata11Bonglee Kim12Rosy Iara Maciel Azambuja Ribeiro13Rony Abdi Syahputra14Department of Biological Sciences, Faculty of Sciences and Technology, State Islamic University of Sunan Kalijaga (UIN Sunan Kalijaga), Yogyakarta, 55281, IndonesiaDepartment of Biological Sciences, Faculty of Sciences and Technology, State Islamic University of Sunan Kalijaga (UIN Sunan Kalijaga), Yogyakarta, 55281, IndonesiaDepartment of Neurology, Faculty of Medicine, Universitas Indonesia - Dr. Cipto Mangunkusumo National Hospital, Jakarta, 10430, IndonesiaDepartment of Biochemistry and Biomolecular, Faculty of Medicine, University of Brawijaya, Malang, 65145, IndonesiaDepartment of Nutrition, Faculty of Health Science, Muhammadiyah Manado University, Manado, 95249, IndonesiaDivision of Clinical Nutrition, Department of Nutrition, Faculty of Medicine, Hasanuddin University, Makassar, 90245, IndonesiaDepartment of Biotechnology, Faculty of Biotechnology, Atma Jaya Catholic University of Indonesia, Jakarta, 12930, IndonesiaDivision of Applied Nutrition, Department of Community Nutrition, Faculty of Human Ecology, IPB University, West Java, Bogor, 16680, IndonesiaDepartment of Biology, Faculty of Mathematics and Natural Sciences, Universitas Sam Ratulangi, Manado, 95115, IndonesiaFood Science Program, Department of Chemistry, Institute of Biochemistry, Carleton University, 1125 Colonel by Drive, Ottawa, K1S 5B6, ON, CanadaDepartment of Food Science, Faculty of Food Science and Technology, Universiti Putra Malaysia, Selangor, UPM Serdang, 43400, MalaysiaInternal Medicine, Hermina Pasuruan Hospital, Pasuruan, 67181, East Java, IndonesiaDepartment of Pathology, College of Korean Medicine, Kyung Hee University, Seou, 02447, Republic of KoreaExperimental Pathology Laboratory, Midwest Campus, Federal University of São João del-Rei, Divinópolis, BrazilDepartment of Pharmacology, Faculty of Pharmacy, Universitas Sumatera Utara, Medan, 20155, Indonesia; Corresponding author.The discovery of new molecules from natural sources for the treatment of tumors such as breast cancers is of importance for the development of functional foods and to the pharmaceutical industry. A natural resource with potential activity against breast cancer is forest onion, Eleutherine bulbosa (Mill.) Urb., but the identity of its active constituents and their mechanisms of action remain unexplored. Therefore, this study focuses on metabolite profiling, in silico or pharmacoinformatic activity and mechanisms, as well as advanced validation on in vitro cell lines. Ten compounds identified in E. bulbosa bulb ethanolic extract (EBE) showed cancer receptor and radical inhibitory activity via network pharmacology and molecular docking simulation. The most promising compound was avenasterol binding PARP-1, HER2, iNOS receptors with values of −11.26, −8.34, and −9.17 μg/mL, respectively. EBE and avenasterol had a smaller EC50 value, or higher potency, than the control antioxidant Trolox in radical scavenging tests with ABTS and DPPH. In line with the in silico study, EBE and avenasterol showed antiproliferative activity against human breast cancer MCF-7 with LD50 217.8 μg/mL, with relatively low cytotoxicity to normal MCF-10A cells (LD50 > 1000 μg/mL). The antiproliferative mechanism of EBE on MCF-7 was associated with downregulation of TGF-β, HER2, PI3K, and AKT which are known tumor activators. Significant (p < 0.05) upregulation of tumor suppressor gene miR-29a-3p in MCF-7 was observed after treatment with EBE in a dose-dependent manner.http://www.sciencedirect.com/science/article/pii/S2666154324003995AnticancerNatural productFunctional foodAvenasterolPARP1MCF-7
spellingShingle Fahrul Nurkolis
Isma Kurniatanty
Elvan Wiyarta
Happy Kurnia Permatasari
Nelly Mayulu
Nurpudji Astuti Taslim
Raymond Rubianto Tjandrawinata
Hardinsyah Hardinsyah
Trina Ekawati Tallei
Apollinaire Tsopmo
Son Radu
Edwin Hadinata
Bonglee Kim
Rosy Iara Maciel Azambuja Ribeiro
Rony Abdi Syahputra
Identification of novel functional compounds from forest onion and its biological activities against breast cancer
Journal of Agriculture and Food Research
Anticancer
Natural product
Functional food
Avenasterol
PARP1
MCF-7
title Identification of novel functional compounds from forest onion and its biological activities against breast cancer
title_full Identification of novel functional compounds from forest onion and its biological activities against breast cancer
title_fullStr Identification of novel functional compounds from forest onion and its biological activities against breast cancer
title_full_unstemmed Identification of novel functional compounds from forest onion and its biological activities against breast cancer
title_short Identification of novel functional compounds from forest onion and its biological activities against breast cancer
title_sort identification of novel functional compounds from forest onion and its biological activities against breast cancer
topic Anticancer
Natural product
Functional food
Avenasterol
PARP1
MCF-7
url http://www.sciencedirect.com/science/article/pii/S2666154324003995
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