Naringenin induces mitochondria-mediated apoptosis and endoplasmic reticulum stress by regulating MAPK and AKT signal transduction pathways in endometriosis cells

Sunwoo Park, Whasun Lim, Fuller W Bazer, Gwonhwa Song
Molecular human reproduction · 2017 · vol. 23(12) , pp. 842–854 · doi:10.1093/molehr/gax057 · PMID:29121349 · W2767758085
article OA: bronze CC0 ⤵ 27 in-corpus citations
📄 Open PDF View on OpenAlex View on PubMed View at publisher
⚙ AI-generated summary by claude@2026-06, 2026-06-07 ⓘ

Naringenin suppresses endometriosis cell proliferation and induces apoptosis by regulating MAPK and AKT pathways, leading to mitochondrial dysfunction and endoplasmic reticulum stress.

One-sentence paraphrase of the abstract; not a substitute for reading it. No clinical advice. How this works

Abstract

STUDY QUESTION: Does the flavonoid naringenin inhibit proliferation of human endometriosis cells? SUMMARY ANSWER: Naringenin suppresses proliferation and increases apoptosis via depolarization of mitochondrial membrane potential and generation of reactive oxygen species (ROS) in human endometriosis cells. WHAT IS KNOWN ALREADY: For management of endometriosis, hormonal therapy is commonly used to decrease production of estrogens by the ovaries, but that has limitations including undesirable side effects with long-term therapies. To overcome these limitations, it is important to discover novel compounds which have no adverse effects, but inhibit expression of target molecules involved in the pathogenesis of endometriosis. STUDY DESIGN SIZE, DURATION: Well-established endometriosis cell lines (VK2/E6E7 and End1/E6E7) were purchased from the American Type Culture Collection. Effects of naringenin on VK2/E6E7 and End1/E6E7 cells were assessed in diverse assays in a dose- and time-dependent manner. PARTICIPANTS/MATERIALS, SETTING, METHODS: Effects of naringenin on viability, apoptosis (Annexin V expression, propidium iodide staining, TUNEL and invasion assays), mitochondria-mediated apoptosis, production of ROS and endoplasmic reticulum (ER) stress proteins of VK2/E6E7 and End1/E6E7 cells were determined. Signal transduction pathways in VK2/E6E7 and End1/E6E7 cells in response to naringenin were determined by western blot analyses. MAIN RESULTS AND THE ROLE OF CHANCE: In the present study, we demonstrated that naringenin suppressed proliferation and increased apoptosis through depolarization of mitochondrial membrane potential and inducing pro-apoptotic proteins, Bax and Bak, in both endometriosis cell lines. In addition, naringenin increased ROS, ER stress, through activation of eIF2α and IRE1α, GADD153 and GRP78 proteins in a dose-dependent manner. Furthermore, the induction of apoptosis by naringenin involved activation of MAPK and inactivation of PI3K pathways in VK2/E6E7 and End1/E6E7 cells. LIMITATIONS REASONS FOR CAUTION: Lack of in vivo animal studies is a major limitation of this research. Effectiveness of naringenin to induce apoptosis of human endometriosis cells requires further investigation. WIDER IMPLICATIONS OF THE FINDINGS: Our results suggest that naringenin is a promising therapeutic compound for treatment of endometriosis in women. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by grants from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (No. HI15C0810 awarded to G.S. and HI17C0929 awarded to W.L.). The authors declare that there are no conflicts of interest.

My notes (saved in your browser only)

Condition tags

mesh:D004715endometriosis

MeSH descriptors

Endoplasmic Reticulum Stress Estrogen Antagonists Flavanones Mitochondria Mitogen-Activated Protein Kinases Stromal Cells Annexin A5 Annexin A5 Annexin A5 Apoptosis Apoptosis bcl-2-Associated X Protein bcl-2-Associated X Protein bcl-2-Associated X Protein bcl-2-Associated X Protein bcl-2 Homologous Antagonist-Killer Protein bcl-2 Homologous Antagonist-Killer Protein bcl-2 Homologous Antagonist-Killer Protein bcl-2 Homologous Antagonist-Killer Protein Cell Line

Citation neighborhood

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

References (49)

Cited by (27)

Source provenance

europepmc
last seen: 2026-06-04T01:30:01.192114+00:00
openalex
last seen: 2026-06-04T00:00:01.174412+00:00
pubmed
last seen: 2026-05-13T22:20:07.505861+00:00
License: CC0 · commercial use OK