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Coenzyme Q0 defeats NLRP3-mediated inflammation, EMT/metastasis, and Warburg effects by inhibiting HIF-1α expression in human triple-negative breast cancer cells

  • Molecular Toxicology
  • Published:
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Abstract

Coenzyme Q0 (CoQ0) is a derivative quinone from Antrodia camphorata (AC) that exerts anticancer activities. This study examined the anticancer attributes of CoQ0 (0–4 µM) on inhibited anti-EMT/metastasis and NLRP3 inflammasome, and altered Warburg effects via HIF-1α inhibition in triple-negative breast cancer (MDA-MB-231 and 468) cells. MTT assay, cell migration/invasion assays, Western blotting, immunofluorescence, metabolic reprogramming, and LC–ESI-MS were carried out to assess the therapy potential of CoQ0. CoQ0 inhibited HIF-1α expression and suppressed the NLRP3 inflammasome and ASC/caspase-1 expression, followed by downregulation of IL-1β and IL-18 expression in MDA-MB-231 and 468 cells. CoQ0 ameliorated cancer stem-like markers by decreasing CD44 and increasing CD24 expression. Notably, CoQ0 modulated EMT by upregulating the epithelial marker E-cadherin and downregulating the mesenchymal marker N-cadherin. CoQ0 inhibited glucose uptake and lactate accumulation. CoQ0 also inhibited HIF-1α downstream genes involved in glycolysis, such as HK-2, LDH-A, PDK-1, and PKM-2 enzymes. CoQ0 decreased extracellular acidification rate (ECAR), glycolysis, glycolytic capacity, and glycolytic reserve in MDA-MB-231 and 468 cells under normoxic and hypoxic (CoCl2) conditions. CoQ0 inhibited the glycolytic intermediates lactate, FBP, and 2/3-PG, and PEP levels. CoQ0 increased oxygen consumption rate (OCR), basal respiration, ATP production, maximal respiration, and spare capacity under normoxic and hypoxic (CoCl2) conditions. CoQ0 increased TCA cycle metabolites, such as citrate, isocitrate, and succinate. CoQ0 inhibited aerobic glycolysis and enhanced mitochondrial oxidative phosphorylation in TNBC cells. Under hypoxic conditions, CoQ0 also mitigated HIF-1α, GLUT1, glycolytic-related (HK-2, LDH-A, and PFK-1), and metastasis-related (E-cadherin, N-cadherin, and MMP-9) protein or mRNA expression in MDA-MB-231 and/or 468 cells. Under LPS/ATP stimulation, CoQ0 inhibited NLRP3 inflammasome/procaspase-1/IL-18 activation and NFκB/iNOS expression. CoQ0 also hindered LPS/ATP-stimulated tumor migration and downregulated LPS/ATP-stimulated N-cadherin and MMP-2/-9 expression. The present study revealed that suppression of HIF-1α expression caused by CoQ0 may contribute to inhibition of NLRP3-mediated inflammation, EMT/metastasis, and Warburg effects of triple-negative breast cancers.

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Data availability

The dataset used and/or analysed during the current study are available from the corresponding author on reasonable request.

Abbreviations

AC:

Antrodia camphorata

CoQ0 :

Coenzyme Q0

TNBC:

Triple-negative breast cancer

EMT:

Epithelial–mesenchymal transition

HIF-1α:

Hypoxia-inducible factor-1α

DMEM:

Dulbecco’s modified Eagle’s medium

DAPI:

Diamidino-2-phenylindole dihydrochloride

NLRP3:

NLR family pyrin domain containing 3

ASC:

Apoptosis-associated speck-like protein

FCCP:

Carbonyl cyanide-p-(trifluoromethoxy) phenylhydrazone

2-NBDG:

2-Deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl) amino]-D-glucose

2-DG:

2-Deoxyglucose

ECAR:

Extracellular acidification rate

OCR:

Oxygen consumption rate

UPLC:

Ultra-performance liquid chromatography

RPLC:

Reversed-phase liquid chromatography

HK-2:

Hexokinase 2

LDH-A:

Lactate dehydrogenase A

PDK-1:

Pyruvate dehydrogenase kinase 1

PKM-2:

Pyruvate kinase M 2

PFK-1:

Phosphofructokinase 1

GLUT1:

Glucose transporter 1

FBP:

Fructose 1,6-bisphosphate

2/3-PG:

2/3-Phosphoglycerate

PEP:

Phosphoenolpyruvate

ALDH1:

Aldehyde dehydrogenase 1

References

  • Armstrong JS, Whiteman M, Rose P, Jones DP (2003) The coenzyme Q10 analog decylubiquinone inhibits the redox-activated mitochondrial permeability transition: role of mitochondrial respiratory complex III. J Biol Chem 278(49):49079–49084

    Article  CAS  PubMed  Google Scholar 

  • Balamurugan K (2016) HIF-1 at the crossroads of hypoxia, inflammation, and cancer. Int J Cancer 138(5):1058–1066

    Article  CAS  PubMed  Google Scholar 

  • Barriga EH, Maxwell PH, Reyes AE, Mayor R (2013) The hypoxia factor Hif-1α controls neural crest chemotaxis and epithelial to mesenchymal transition. J Cell Biol 201(5):759–776

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Broz P, Monack DM (2011) Molecular mechanisms of inflammasome activation during microbial infections. Immunol Rev 243(1):174–190

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Courtnay R, Ngo DC, Malik N, Ververis K, Tortorella SM, Karagiannis TC (2015) Cancer metabolism and the Warburg effect: the role of HIF-1 and PI3K. Mol Biol Rep 42(4):841–851

    Article  CAS  PubMed  Google Scholar 

  • Fink SL, Cookson BT (2005) Apoptosis, pyroptosis, and necrosis: mechanistic description of dead and dying eukaryotic cells. Infect Immun 73(4):1907–1916

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ganapathy-Kanniappan S (2018) Molecular intricacies of aerobic glycolysis in cancer: current insights into the classic metabolic phenotype. Crit Rev Biochem Mol Biol 53(6):667–682

    Article  CAS  PubMed  Google Scholar 

  • Geethangili M, Tzeng Y-M (2011) Review of pharmacological effects of Antrodia camphorata and its bioactive compounds. Evid Based Complement Altern Med. https://doi.org/10.1093/ecam/nep108

    Article  Google Scholar 

  • Ghuwalewala S, Ghatak D, Das P et al (2016) CD44highCD24low molecular signature determines the cancer stem cell and EMT phenotype in oral squamous cell carcinoma. Stem Cell Res 16(2):405–417

    Article  CAS  PubMed  Google Scholar 

  • Grebe A, Hoss F, Latz E (2018) NLRP3 inflammasome and the IL-1 pathway in atherosclerosis. Circ Res 122(12):1722–1740

    Article  CAS  PubMed  Google Scholar 

  • Hamarsheh S, Zeiser R (2020) NLRP3 inflammasome activation in cancer: a double-edged sword. Front Immunol 11:1444

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ho M-L, Hsiao Y-H, Su S-Y, Chou M-C, Liaw Y-P (2015) Mortality of breast cancer in Taiwan, 1971–2010: Temporal changes and an age–period–cohort analysis. J Obstet Gynaecol 35(1):60–63

    Article  PubMed  Google Scholar 

  • Hseu Y-C, Yang H-L, Lai Y-C, Lin J-G, Chen G-W, Chang Y-H (2004) Induction of apoptosis by Antrodia camphorata in human premyelocytic leukemia HL-60 cells. Nutr Cancer 48(2):189–197

    Article  PubMed  Google Scholar 

  • Hseu Y-C, Chen S-C, Tsai P-C et al (2007) Inhibition of cyclooxygenase-2 and induction of apoptosis in estrogen-nonresponsive breast cancer cells by Antrodia camphorata. Food Chem Toxicol 45(7):1107–1115

    Article  CAS  PubMed  Google Scholar 

  • Hseu Y-C, Huang H-C, Hsiang C-Y (2010) Antrodia camphorata suppresses lipopolysaccharide-induced nuclear factor-κB activation in transgenic mice evaluated by bioluminescence imaging. Food Chem Toxicol 48(8–9):2319–2325

    Article  CAS  PubMed  Google Scholar 

  • Hseu Y-C, Thiyagarajan V, Tsou H-T et al (2016) In vitro and in vivo anti-tumor activity of CoQ0 against melanoma cells: inhibition of metastasis and induction of cell-cycle arrest and apoptosis through modulation of Wnt/β-catenin signaling pathways. Oncotarget 7(16):22409

    Article  PubMed  PubMed Central  Google Scholar 

  • Hseu Y-C, Chao Y-H, Lin K-Y et al (2017) Antrodia camphorata inhibits metastasis and epithelial-to-mesenchymal transition via the modulation of claudin-1 and Wnt/β-catenin signaling pathways in human colon cancer cells. J Ethnopharmacol 208:72–83

    Article  PubMed  Google Scholar 

  • Hseu YC, Tseng YF, Pandey S, Shrestha S, Lin KY, Lin CW, Lee CC, Huang ST, Yang HL (2022) Coenzyme Q0 inhibits NLRP3 inflammasome activation through mitophagy induction in LPS/ATP-stimulated macrophages. Oxid Med Cell Longev. 2022:4266214. https://doi.org/10.1155/2022/4266214

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hughes MM, O’Neill LA (2018) Metabolic regulation of nlrp 3. Immunol Rev 281(1):88–98

    Article  CAS  PubMed  Google Scholar 

  • Iqbal MA, Chattopadhyay S, Siddiqui FA et al (2021) Silibinin induces metabolic crisis in triple-negative breast cancer cells by modulating EGFR-MYC-TXNIP axis: potential therapeutic implications. FEBS J 288(2):471–485

    Article  CAS  PubMed  Google Scholar 

  • Jia J, Liu Y, Zhang X, Liu X, Qi J (2013) Regulation of iNOS expression by NF-κB in human lens epithelial cells treated with high levels of glucose. Invest Ophthalmol vis Sci 54(7):5070–5077

    Article  PubMed  Google Scholar 

  • Jin J, Qiu S, Wang P et al (2019) Cardamonin inhibits breast cancer growth by repressing HIF-1α-dependent metabolic reprogramming. J Exp Clin Cancer Res 38(1):1–16

    Article  Google Scholar 

  • Kalluri R, Weinberg RA (2009) The basics of epithelial-mesenchymal transition. J Clin Investig 119(6):1420–1428

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kawasaki T, Kawai T (2014) Toll-like receptor signaling pathways. Front Immunol. https://doi.org/10.3389/fimmu.2014.00461

    Article  PubMed  PubMed Central  Google Scholar 

  • Khan A, Siddiqui S, Husain SA, Mazurek S, Iqbal MA (2021) Phytocompounds targeting metabolic reprogramming in cancer: an assessment of role, mechanisms, pathways, and therapeutic relevance. J Agric Food Chem 69(25):6897–6928

    Article  CAS  Google Scholar 

  • Klück V, Tim L, Janssen M et al (2020) Dapansutrile, an oral selective NLRP3 inflammasome inhibitor, for treatment of gout flares: an open-label, dose-adaptive, proof-of-concept, phase 2a trial. Lancet Rheumatol 2(5):e270–e280

    Article  PubMed  PubMed Central  Google Scholar 

  • Knudsen CA, Tappel AL, North JA (1996) Multiple antioxidants protect against heme protein and lipid oxidation in kidney tissue. Free Radical Biol Med 20(2):165–173

    Article  CAS  Google Scholar 

  • Kumar Jha M, Jeon S, Suk K (2012) Pyruvate dehydrogenase kinases in the nervous system: their principal functions in neuronal-glial metabolic interaction and neuro-metabolic disorders. Curr Neuropharmacol 10(4):393–403

    Article  Google Scholar 

  • Latz E, Xiao TS, Stutz A (2013) Activation and regulation of the inflammasomes. Nat Rev Immunol 13(6):397–411

    Article  CAS  PubMed  Google Scholar 

  • Lee HE, Lee JY, Yang G et al (2019) Inhibition of NLRP3 inflammasome in tumor microenvironment leads to suppression of metastatic potential of cancer cells. Sci Rep 9(1):1–9

    Google Scholar 

  • Li Q, Mattingly RR (2008) Restoration of E-cadherin cell-cell junctions requires both expression of E-cadherin and suppression of ERK MAP kinase activation in Ras-transformed breast epithelial cells. Neoplasia 10(12):1444–1458

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li S, Pritchard DM, Yu L-G (2022a) Regulation and function of matrix metalloproteinase-13 in cancer progression and metastasis. Cancers 14(13):3263

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li Z, Xia Z, Yu Y et al (2022b) A pyroptosis-associated signature plays a role in prognosis prediction in clear cell renal cell carcinoma. BMC Med Genom 15(1):1–17

    Article  Google Scholar 

  • Liang CC, Park AY, Guan JL (2007) In vitro scratch assay: a convenient and inexpensive method for analysis of cell migration in vitro. Nat Protoc 2(2):329–333. https://doi.org/10.1038/nprot.2007.30

    Article  CAS  PubMed  Google Scholar 

  • Liberti MV, Locasale JW (2016) The Warburg effect: how does it benefit cancer cells? Trends Biochem Sci 41(3):211–218

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lu H, Lyu Y, Tran L et al (2021) HIF-1 recruits NANOG as a coactivator for TERT gene transcription in hypoxic breast cancer stem cells. Cell Rep 36(13):109757

    Article  CAS  PubMed  Google Scholar 

  • MacDonald MJ, Husain RD, Hoffmann-Benning S, Baker TR (2004) Immunochemical identification of coenzyme Q0-dihydrolipoamide adducts in the E2 components of the α-ketoglutarate and pyruvate dehydrogenase complexes partially explains the cellular toxicity of coenzyme Q0. J Biol Chem 279(26):27278–27285

    Article  CAS  PubMed  Google Scholar 

  • Marandi Y, Hashemzade S, Tayebinia H, Karimi J, Zamani A, Khodadadi I (2021) NLRP3-inflammasome activation is associated with epithelial-mesenchymal transition and progression of colorectal cancer. Iran J Basic Med Sci 24(4):483

    PubMed  PubMed Central  Google Scholar 

  • Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65(1–2):55–63

    Article  CAS  PubMed  Google Scholar 

  • Mrozik KM, Blaschuk OW, Cheong CM, Zannettino ACW, Vandyke K (2018) N-cadherin in cancer metastasis, its emerging role in haematological malignancies and potential as a therapeutic target in cancer. BMC Cancer 18(1):1–16

    Article  Google Scholar 

  • Nagao A, Kobayashi M, Koyasu S, Chow CC, Harada H (2019) HIF-1-dependent reprogramming of glucose metabolic pathway of cancer cells and its therapeutic significance. Int J Mol Sci 20(2):238

    Article  PubMed  PubMed Central  Google Scholar 

  • Nakamura M, Tokura Y (2011) Epithelial–mesenchymal transition in the skin. J Dermatol Sci 61(1):7–13

    Article  CAS  PubMed  Google Scholar 

  • Nikonovas T, Spessa A, Doerr SH, Clay GD, Mezbahuddin S (2020) Near-complete loss of fire-resistant primary tropical forest cover in Sumatra and Kalimantan. Commun Earth Environ 1(1):1–8

    Article  Google Scholar 

  • Oh YS, Kim HY, Song I-C et al (2012) Hypoxia induces CXCR4 expression and biological activity in gastric cancer cells through activation of hypoxia-inducible factor-1α. Oncol Rep 28(6):2239–2246

    Article  CAS  PubMed  Google Scholar 

  • Ramos Solis N, Yeh ES (2022) HUNK regulation of interleukin 4 in triple negative breast cancer. FASEB J. https://doi.org/10.1096/fasebj.2022.36.S1.R2558

    Article  Google Scholar 

  • Rana NK, Singh P, Koch B (2019) CoCl2 simulated hypoxia induce cell proliferation and alter the expression pattern of hypoxia associated genes involved in angiogenesis and apoptosis. Biol Res 52(1):1–13

    Article  Google Scholar 

  • Shibata S, Sogabe S, Miwa M et al (2021) Identification of the first highly selective inhibitor of human lactate dehydrogenase B. Sci Rep 11(1):1–12

    Article  Google Scholar 

  • Sibiak R, Ozegowska K, Wender-Ozegowska E, Gutaj P, Mozdziak P, Kempisty B (2022) Fetomaternal expression of glucose transporters (GLUTs). Biochem Cell Clin Aspects 14(10):2025

    CAS  Google Scholar 

  • Siddiqui FA, Prakasam G, Chattopadhyay S et al (2018) Curcumin decreases Warburg effect in cancer cells by down-regulating pyruvate kinase M2 via mTOR-HIF1α inhibition. Sci Rep 8(1):1–9

    Article  CAS  Google Scholar 

  • Sun Q, Scott MJ (2016) Caspase-1 as a multifunctional inflammatory mediator: noncytokine maturation roles. J Leukoc Biol 100(5):961–967

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sun X, Wang M, Wang M et al (2020) Metabolic reprogramming in triple-negative breast cancer. Front Oncol 10:428

    Article  PubMed  PubMed Central  Google Scholar 

  • Tomita H, Tanaka K, Tanaka T (2016) Hara A Aldehyde dehydrogenase 1A1 in stem cells and cancer. Oncotarget 7:11018–11032

    Article  PubMed  PubMed Central  Google Scholar 

  • Vadivalagan C, Krishnan A, Chen S-J et al (2022) The Warburg effect in osteoporosis: cellular signaling and epigenetic regulation of energy metabolic events to targeting the osteocalcin for phenotypic alteration. Cell Signal 100:110488

    Article  CAS  PubMed  Google Scholar 

  • Walsh EM, Keane MM, Wink DA, Callagy G, Glynn SA (2016) Review of triple negative breast cancer and the impact of inducible nitric oxide synthase on tumor biology and patient outcomes. Crit Rev Oncog 21(5–6):333

    Article  PubMed  PubMed Central  Google Scholar 

  • Wang H-M, Yang H-L, Thiyagarajan V et al (2017) Coenzyme Q0 enhances ultraviolet B-induced apoptosis in human estrogen receptor-positive breast (MCF-7) cancer cells. Integr Cancer Ther 16(3):385–396

    Article  PubMed  Google Scholar 

  • Wang S, Liu G, Li Y, Pan Y (2022) Metabolic reprogramming induces macrophage polarization in the tumor microenvironment. Front Immunol. https://doi.org/10.3389/fimmu.2022.840029

    Article  PubMed  PubMed Central  Google Scholar 

  • Warner S, Auger K, Libby P (1987) Interleukin 1 induces interleukin 1. II. Recombinant human interleukin 1 induces interleukin 1 production by adult human vascular endothelial cells. J Immunol 139(6):1911–1917

    Article  CAS  PubMed  Google Scholar 

  • Webb BA, Forouhar F, Szu F-E, Seetharaman J, Tong L, Barber DL (2015) Structures of human phosphofructokinase-1 and atomic basis of cancer-associated mutations. Nature 523(7558):111–114

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Welch DR, Hurst DR (2019) Defining the hallmarks of metastasis. Can Res 79(12):3011–3027

    Article  CAS  Google Scholar 

  • Weljie AM, Jirik FR (2011) Hypoxia-induced metabolic shifts in cancer cells: moving beyond the Warburg effect. Int J Biochem Cell Biol 43(7):981–989

    Article  CAS  PubMed  Google Scholar 

  • Yang H-L, Hseu Y-C, Chen J-Y et al (2006) Antrodia camphorata in submerged culture protects low density lipoproteins against oxidative modification. Am J Chin Med 34(02):217–231

    Article  PubMed  Google Scholar 

  • Yang J-S, Gad H, Lee SY et al (2008a) A role for phosphatidic acid in COPI vesicle fission yields insights into Golgi maintenance. Nat Cell Biol 10(10):1146–1153

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang M-H, Wu M-Z, Chiou S-H et al (2008b) Direct regulation of TWIST by HIF-1α promotes metastasis. Nat Cell Biol 10(3):295–305

    Article  CAS  PubMed  Google Scholar 

  • Yang H-L, Kuo Y-H, Tsai C-T et al (2011) Anti-metastatic activities of Antrodia camphorata against human breast cancer cells mediated through suppression of the MAPK signaling pathway. Food Chem Toxicol 49(1):290–298

    Article  CAS  PubMed  Google Scholar 

  • Yang H-L, Korivi M, Lin M-W, Chen S-C, Chou C-W, Hseu Y-C (2015) Anti-angiogenic properties of coenzyme Q0 through downregulation of MMP-9/NF-κB and upregulation of HO-1 signaling in TNF-α-activated human endothelial cells. Biochem Pharmacol 98(1):144–156

    Article  CAS  PubMed  Google Scholar 

  • Yang S-w, Zhang Z-g, Hao Y-x et al (2017) HIF-1α induces the epithelial-mesenchymal transition in gastric cancer stem cells through the Snail pathway. Oncotarget 8(6):9535

    Article  PubMed  PubMed Central  Google Scholar 

  • Yang H-L, Thiyagarajan V, Shen P-C et al (2019a) Anti-EMT properties of CoQ0 attributed to PI3K/AKT/NFKB/MMP-9 signaling pathway through ROS-mediated apoptosis. J Exp Clin Cancer Res 38(1):1–21

    Article  Google Scholar 

  • Yang Q, Liu R, Yu Q, Bi Y, Liu G (2019b) Metabolic regulation of inflammasomes in inflammation. Immunology 157(2):95–109

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang H-L, Tsai C-H, Shrestha S, Lee C-C, Liao J-W, Hseu Y-C (2021) Coenzyme Q0, a novel quinone derivative of Antrodia camphorata, induces ROS-mediated cytotoxic autophagy and apoptosis against human glioblastoma cells in vitro and in vivo. Food Chem Toxicol 155:112384

    Article  CAS  PubMed  Google Scholar 

  • Yang R, Li Y, Wang H, Qin T, Yin X, Ma X (2022) Therapeutic progress and challenges for triple negative breast cancer: targeted therapy and immunotherapy. Mol Biomed 3(1):1–18

    Article  PubMed  PubMed Central  Google Scholar 

  • Yoshida GJ (2015) Metabolic reprogramming: the emerging concept and associated therapeutic strategies. J Exp Clin Cancer Res 34(1):1–10

    Article  Google Scholar 

  • Youm Y-H, Nguyen KY, Grant RW et al (2015) The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome–mediated inflammatory disease. Nat Med 21(3):263–269

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zahid A, Li B, Kombe AJK, Jin T, Tao J (2019) Pharmacological inhibitors of the NLRP3 inflammasome. Front Immunol 10:2538

    Article  PubMed  PubMed Central  Google Scholar 

  • Zahra K, Dey T, Mishra SP, Pandey U (2020) Pyruvate kinase M2 and cancer: the role of PKM2 in promoting tumorigenesis. Front Oncol 10:159

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhou R, Yazdi AS, Menu P, Tschopp J (2011) A role for mitochondria in NLRP3 inflammasome activation. Nature 469(7329):221–225. https://doi.org/10.1038/nature09663

    Article  CAS  PubMed  Google Scholar 

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Funding

This study was supported by the Ministry of Science and Technology, Asia University, and China Medical University, Taiwan (grants MOST-109-2320-B-039-057-MY3 and MOST-110-2320-B-039-046-MY3, CMU110-MF-13). This work was financially supported by the “Chinese Medicine Research Center, China Medical University” from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education (MOE) in Taiwan (CMRC-CHM-1).

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Authors and Affiliations

  1. Institute of Nutrition, College of Health Care, China Medical University, No. 100, Section 1, Jingmao Road, Beitun, Taichung, 406040, Taiwan

    Hsin-Ling Yang, Ping-Yu Lin & Yi-An Lin

  2. Department of Cosmeceutics, College of Pharmacy, China Medical University, No. 100, Section 1, Jingmao Road, Beitun, Taichung, 406040, Taiwan

    Chithravel Vadivalagan & You-Cheng Hseu

  3. Department of Medical Research, Chi-Mei Medical Center, Tainan, 710, Taiwan

    Kai-Yuan Lin

  4. Department of Biotechnology, Chia Nan University of Pharmacy and Science, Tainan, 71710, Taiwan

    Kai-Yuan Lin

  5. Department of Health and Nutrition Biotechnology, Asia University, Taichung, 41354, Taiwan

    You-Cheng Hseu

  6. Chinese Medicine Research Center, China Medical University, Taichung, 40402, Taiwan

    You-Cheng Hseu

  7. Research Center of Chinese Herbal Medicine, China Medical University, Taichung, 40402, Taiwan

    You-Cheng Hseu

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Contributions

Conceived and designed the experiments: HLY, KYL, and YCH conceived the idea. HLY, PYL, and YCH performed the experiments. PYL and KYL analyzed the data. CV and YCH wrote the paper. All authors read and approved the final manuscript.

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Correspondence to You-Cheng Hseu.

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Yang, HL., Lin, PY., Vadivalagan, C. et al. Coenzyme Q0 defeats NLRP3-mediated inflammation, EMT/metastasis, and Warburg effects by inhibiting HIF-1α expression in human triple-negative breast cancer cells. Arch Toxicol 97, 1047–1068 (2023). https://doi.org/10.1007/s00204-023-03456-w

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