Evidence map›Paper›PMID 35056691›Full record

ArticleMolecules (Basel, Switzerland)2022

Naringenin Induces ROS-Mediated ER Stress, Autophagy, and Apoptosis in Human Osteosarcoma Cell Lines.

Chiang-Wen Lee, Cathy Chia-Yu Huang, Miao-Ching Chi, Kuan-Han Lee, Kuo-Ti Peng, Mei-Ling Fang, Yao-Chang Chiang, Ju-Fang Liu

Open access · goldAbstract read
In one paragraph

Article in Molecules (Basel, Switzerland), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
5.9field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

22 citing papers in PubMed, 40 citations in OpenAlex.

  1. Review
  2. Naringenin Nanocrystals Containing PluronicGels (Basel, Switzerland) · 2026
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  9. Article
  10. Naringin vs.Antioxidants (Basel, Switzerland) · 2025
    Article
  11. Article
  12. Review
  13. An Updated Review Summarizing the Anticancer Potential of Naringenin.Endocrine, metabolic & immune disorders drug targets · 2025
    Review
  14. Article
  15. Article
  16. Review
  17. Review
  18. Multi-Anticancer Activities of Phytoestrogens in Human Osteosarcoma.International journal of molecular sciences · 2023
    Review
  19. Article
  20. Redox Active Molecules in Cancer Treatments.Molecules (Basel, Switzerland) · 2023
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 7 institutions in 1 country.

Chiang-Wen LeeDepartment of Nursing, Division of Basic Medical Sciences, Chronic Diseases and Health Promotion Research Center and Research Center for Chinese Herbal Medicine, Chang Gung University of Science and Technology, Puzi City 61363, Taiwan.
Cathy Chia-Yu HuangDepartment of Life Sciences, National Central University, Taoyuan City 320317, Taiwan.
Miao-Ching ChiDepartment of Respiratory Care, Chang Gung University of Science and Technology, Puzi City 613, Taiwan.
Kuan-Han LeeDivision of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan.
Kuo-Ti PengDepartment of Orthopaedic Surgery, Chang Gung Memorial Hospital, Puzi City 61363, Taiwan.
Mei-Ling FangCenter for Environmental Toxin and Emerging-Contaminant Research, Cheng Shiu University, Kaohsiung 833, Taiwan.
Yao-Chang ChiangDepartment of Nursing, Division of Basic Medical Sciences, Chronic Diseases and Health Promotion Research Center and Research Center for Chinese Herbal Medicine, Chang Gung University of Science and Technology, Puzi City 61363, Taiwan.ORCID 0000-0002-7619-1902
Ju-Fang LiuDepartment of Medical Research, China Medical University Hospital, China Medical University, Taichung 40402, Taiwan.
Chang Gung University of Science and Technology · TWChang Gung Memorial Hospital · TWCheng Shiu University · TWChina Medical University · TWKaohsiung Chang Gung Memorial Hospital · TWMing Chi University of Technology · TWNational Central University · TW

Funding

Chang Gung Medical Research Program Foundation CMRPF6K0041Chang Gung University of Science Foundation ZRRPF3L0091Chang Gung University of Science Foundation ZRRPF6L0011Taipei Medical University TMU108-AE1-B47The Ministry of Science and Technology MOST-106-2314-B-038-099-MY3
6 · The paper itself

Abstract

Osteosarcoma, a primary bone tumor, responds poorly to chemotherapy and radiation therapy in children and young adults; hence, as the basis for an alternative treatment, this study investigated the cytotoxic and antiproliferative effects of naringenin on osteosarcoma cell lines, HOS and U2OS, by using cell counting kit-8 and colony formation assays. DNA fragmentation and the increase in the G2/M phase in HOS and U2OS cells upon treatment with various naringenin concentrations were determined by using the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay and Annexin V/propidium iodide double staining, respectively. Flow cytometry was performed, and 2',7'-dichlorodihydrofluorescein diacetate, JC-1, and Fluo-4 AM ester probes were examined for reactive oxygen species (ROS) generation, mitochondrial membrane potential, and intracellular calcium levels, respectively. Caspase activation, cell cycle, cytosolic and mitochondrial, and autophagy-related proteins were determined using western blotting. The results indicated that naringenin significantly inhibited viability and proliferation of osteosarcoma cells in a dose-dependent manner. In addition, naringenin induced cell cycle arrest in osteosarcoma cells by inhibiting cyclin B1 and cyclin-dependent kinase 1 expression and upregulating p21 expression. Furthermore, naringenin significantly inhibited the growth of osteosarcoma cells by increasing the intracellular ROS level. Naringenin induced endoplasmic reticulum (ER) stress-mediated apoptosis through the upregulation of ER stress markers, GRP78 and GRP94. Naringenin caused acidic vesicular organelle formation and increased autophagolysosomes, microtubule-associated protein-light chain 3-II protein levels, and autophagy. The findings suggest that the induction of cell apoptosis, cell cycle arrest, and autophagy by naringenin through mitochondrial dysfunction, ROS production, and ER stress signaling pathways contribute to the antiproliferative effect of naringenin on osteosarcoma cells.

Indexed as

ApoptosisAutophagyCell ProliferationEndoplasmic Reticulum Chaperone BiPEndoplasmic Reticulum StressFlavanonesMembrane Potential, MitochondrialOsteosarcomaReactive Oxygen SpeciesBone NeoplasmsCell Cycle CheckpointsCell Line, TumorCell SurvivalHumansEndoplasmic Reticulum Chaperone BiPFlavanonesHSPA5 protein, humannaringeninReactive Oxygen SpeciesapoptosisautophagyER stressnaringeninosteosarcomaROS

Identifiers

PMID35056691
PMCPMC8781290
OpenAlexW4205801238

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.