Arachidonic acid metabolism as a novel pathogenic factor in gastrointestinal cancers.
Arachidonic acid
Clinical application
Colorectal cancer
Gastric cancer
Liver cancer
Pancreatic cancer
Journal
Molecular and cellular biochemistry
ISSN: 1573-4919
Titre abrégé: Mol Cell Biochem
Pays: Netherlands
ID NLM: 0364456
Informations de publication
Date de publication:
04 Jul 2024
04 Jul 2024
Historique:
received:
27
05
2024
accepted:
25
06
2024
medline:
4
7
2024
pubmed:
4
7
2024
entrez:
4
7
2024
Statut:
aheadofprint
Résumé
Gastrointestinal (GI) cancers are a major global health burden, representing 20% of all cancer diagnoses and 22.5% of global cancer-related deaths. Their aggressive nature and resistance to treatment pose a significant challenge, with late-stage survival rates below 15% at five years. Therefore, there is an urgent need to delve deeper into the mechanisms of gastrointestinal cancer progression and optimize treatment strategies. Increasing evidence highlights the active involvement of abnormal arachidonic acid (AA) metabolism in various cancers. AA is a fatty acid mainly metabolized into diverse bioactive compounds by three enzymes: cyclooxygenase, lipoxygenase, and cytochrome P450 enzymes. Abnormal AA metabolism and altered levels of its metabolites may play a pivotal role in the development of GI cancers. However, the underlying mechanisms remain unclear. This review highlights a unique perspective by focusing on the abnormal metabolism of AA and its involvement in GI cancers. We summarize the latest advancements in understanding AA metabolism in GI cancers, outlining changes in AA levels and their potential role in liver, colorectal, pancreatic, esophageal, gastric, and gallbladder cancers. Moreover, we also explore the potential of targeting abnormal AA metabolism for future therapies, considering the current need to explore AA metabolism in GI cancers and outlining promising avenues for further research. Ultimately, such investigations aim to improve treatment options for patients with GI cancers and pave the way for better cancer management in this area.
Identifiants
pubmed: 38963615
doi: 10.1007/s11010-024-05057-2
pii: 10.1007/s11010-024-05057-2
doi:
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
Références
Gravitz L (2014) Liver cancer. Nature 516(7529):S1
pubmed: 25470192
doi: 10.1038/516S1a
Kim BH, Park JW (2018) Epidemiology of liver cancer in South Korea. Clin Mol Hepatol 24(1):1–9
pubmed: 29249129
doi: 10.3350/cmh.2017.0112
Klein AP (2021) Pancreatic cancer epidemiology: understanding the role of lifestyle and inherited risk factors. Nat Rev Gastroenterol Hepatol 18(7):493–502
pubmed: 34002083
pmcid: 9265847
doi: 10.1038/s41575-021-00457-x
Stoffel EM, Brand RE, Goggins M (2023) Pancreatic cancer: changing epidemiology and new approaches to risk assessment, early detection, and prevention. Gastroenterology 164(5):752–765
pubmed: 36804602
doi: 10.1053/j.gastro.2023.02.012
Arnold M, Abnet CC, Neale RE, Vignat J, Giovannucci EL, McGlynn KA, Bray F (2020) Global burden of 5 major types of gastrointestinal cancer. Gastroenterology 159(1):335–49.e15
pubmed: 32247694
doi: 10.1053/j.gastro.2020.02.068
Cai J, Chen H, Lu M, Zhang Y, Lu B, You L, Zhang T, Dai M, Zhao Y (2021) Advances in the epidemiology of pancreatic cancer: Trends, risk factors, screening, and prognosis. Cancer Lett 520:1
pubmed: 34216688
doi: 10.1016/j.canlet.2021.06.027
Bruix J, Han KH, Gores G, Llovet JM, Mazzaferro V (2015) Liver cancer: approaching a personalized care. J Hepatol 62(1):S144–S156
pubmed: 25920083
pmcid: 4520430
doi: 10.1016/j.jhep.2015.02.007
Zhang XY, Zhang PY (2017) Gastric cancer: somatic genetics as a guide to therapy. J Med Genet 54(5):305–312
pubmed: 27609016
doi: 10.1136/jmedgenet-2016-104171
Alonso S, Saltz L (2021) The landmark series: chemotherapy for non-metastatic colon cancer. Ann Surg Oncol 28(2):995–1001
pubmed: 33230749
doi: 10.1245/s10434-020-09375-9
Venerito M, Link A, Rokkas T, Malfertheiner P (2016) Gastric cancer–clinical and epidemiological aspects. Helicobacter 21:39–44
pubmed: 27531538
doi: 10.1111/hel.12339
Lu L, Mullins CS, Schafmayer C, Zeißig S, Linnebacher M (2021) A global assessment of recent trends in gastrointestinal cancer and lifestyle-associated risk factors. Cancer Commun (Lond) 41(11):1137–1151
pubmed: 34563100
doi: 10.1002/cac2.12220
Chen K, Li Y, Wang B, Yan X, Tao Y, Song W, Xi Z, He K, Xia Q (2023) Patient-derived models facilitate precision medicine in liver cancer by remodeling cell-matrix interaction. Front Immunol 14:1101324
pubmed: 37215109
pmcid: 10192760
doi: 10.3389/fimmu.2023.1101324
Vincent A, Herman J, Schulick R, Hruban RH, Goggins M (2011) Pancreatic cancer. Lancet 378(9791):607–620
pubmed: 21620466
pmcid: 3062508
doi: 10.1016/S0140-6736(10)62307-0
Crew KD, Neugut AI (2006) Epidemiology of gastric cancer. World J Gastroenterol 12(3):354–362
pubmed: 16489633
pmcid: 4066052
doi: 10.3748/wjg.v12.i3.354
Xue C, Li G, Zheng Q, Gu X, Bao Z, Lu J, Li L (2022) The functional roles of the circRNA/Wnt axis in cancer. Mol Cancer 21(1):108
pubmed: 35513849
pmcid: 9074313
doi: 10.1186/s12943-022-01582-0
Chen Y, Chen T, Fang JY (2023) Burden of gastrointestinal cancers in China from 1990 to 2019 and projection through 2029. Cancer Lett 560:216127
pubmed: 36933779
doi: 10.1016/j.canlet.2023.216127
McGiff JC (1987) Arachidonic acid metabolism. Prev Med 16(4):503–509
pubmed: 3114736
doi: 10.1016/0091-7435(87)90064-8
Yang H, Rothenberger E, Zhao T, Fan W, Kelly A, Attaya A, Fan D, Panigrahy D, Deng J (2023) Regulation of inflammation in cancer by dietary eicosanoids. Pharmacol Ther 248:108455
pubmed: 37257760
doi: 10.1016/j.pharmthera.2023.108455
Piomelli D (1993) Arachidonic acid in cell signaling. Curr Opin Cell Biol 5(2):274–280
pubmed: 7685181
doi: 10.1016/0955-0674(93)90116-8
Panagiotopoulos AA, Kalyvianaki K, Castanas E, Kampa M (2018) Eicosanoids in prostate cancer. Cancer Metastasis Rev 37(2–3):237–243
pubmed: 30078159
doi: 10.1007/s10555-018-9750-0
Sausville LN, Williams SM, Pozzi A (2019) Cytochrome P450 epoxygenases and cancer: A genetic and a molecular perspective. Pharmacol Ther 196:183–94
pubmed: 30521883
doi: 10.1016/j.pharmthera.2018.11.009
Borin TF, Angara K, Rashid MH, Achyut BR, Arbab AS (2017) Arachidonic acid metabolite as a novel therapeutic target in breast cancer metastasis. Int J Mol Sci 18:266
doi: 10.3390/ijms18122661
Hyde CA, Missailidis S (2009) Inhibition of arachidonic acid metabolism and its implication on cell proliferation and tumour-angiogenesis. Int Immunopharmacol 9(6):701–715
pubmed: 19239926
doi: 10.1016/j.intimp.2009.02.003
Li X, Chen G, Wang F, Guo X, Zhang R, Liu P, Dong L, Yu W, Wang H, Wang H et al (2023) Oncogenic PIK3CA recruits myeloid-derived suppressor cells to shape the immunosuppressive tumour microenvironment in luminal breast cancer through the 5-lipoxygenase-dependent arachidonic acid pathway. Clin Transl Med 13(11):e1483
pubmed: 37965796
pmcid: 10646754
doi: 10.1002/ctm2.1483
Xu M, Wang X, Li Y, Geng X, Jia X, Zhang L, Yang H (2021) Arachidonic acid metabolism controls macrophage alternative activation through regulating oxidative phosphorylation in PPARγ dependent manner. Front Immunol 12:618501
pubmed: 34149684
pmcid: 8211451
doi: 10.3389/fimmu.2021.618501
Pan P, Qin G, Wang B, Yu H, Chen J, Liu J, Bing K, Shen J, Ren D, Zhao Y et al (2022) HDAC5 loss enhances phospholipid-derived arachidonic acid generation and confers sensitivity to cPLA2 inhibition in pancreatic cancer. Cancer Res 82(24):4542–4554
pubmed: 36102738
pmcid: 9755957
doi: 10.1158/0008-5472.CAN-21-4362
Zhao Z, Liu X, Xiang Y, Hou Z, He K, Zhong G, Hu J, Cai D, Liu Y, Ren J et al (2024) Inhibiting cholesterol de novo synthesis promotes hepatocellular carcinoma progression by upregulating prostaglandin E synthase 2-mediated arachidonic acid metabolism under high fatty acid conditions. Cancer Sci 115(2):477–489
pubmed: 38081591
doi: 10.1111/cas.16035
Xue C, Yao Q, Gu X, Shi Q, Yuan X, Chu Q, Bao Z, Lu J, Li L (2023) Evolving cognition of the JAK-STAT signaling pathway: autoimmune disorders and cancer. Signal Transduct Target Ther 8(1):204
pubmed: 37208335
pmcid: 10196327
doi: 10.1038/s41392-023-01468-7
Hu J, Frömel T, Fleming I (2018) Angiogenesis and vascular stability in eicosanoids and cancer. Cancer Metastasis Rev 37(2–3):425–438
pubmed: 29808461
doi: 10.1007/s10555-018-9732-2
Jones R, Adel-Alvarez LA, Alvarez OR, Broaddus R, Das S (2003) Arachidonic acid and colorectal carcinogenesis. Mol Cell Biochem 253(1–2):141–149
pubmed: 14619964
Wang K, Shi JH, Gao J, Sun Y, Wang Z, Shi X, Guo W, Jin Y, Zhang S (2024) Arachidonic acid metabolism CYP450 pathway is deregulated in hepatocellular carcinoma and associated with microvascular invasion. Cell Biol Int 48(1):31–45
pubmed: 37655528
doi: 10.1002/cbin.12086
Xu C, Gu L, Hu L, Jiang C, Li Q, Sun L, Zhou H, Liu Y, Xue H, Li J et al (2023) FADS1-arachidonic acid axis enhances arachidonic acid metabolism by altering intestinal microecology in colorectal cancer. Nat Commun 14(1):2042
pubmed: 37041160
pmcid: 10090135
doi: 10.1038/s41467-023-37590-x
Lee JY, Nam M, Son HY, Hyun K, Jang SY, Kim JW, Kim MW, Jung Y, Jang E, Yoon SJ et al (2020) Polyunsaturated fatty acid biosynthesis pathway determines ferroptosis sensitivity in gastric cancer. Proc Natl Acad Sci U S A 117(51):32433–32442
pubmed: 33288688
pmcid: 7768719
doi: 10.1073/pnas.2006828117
Brash AR (2001) Arachidonic acid as a bioactive molecule. J Clin Invest 107(11):1339–1345
pubmed: 11390413
pmcid: 209328
doi: 10.1172/JCI13210
Badr KF (1999) Arachidonic acid in cellular activation. Kidney Int 55(5):2070–2071
pubmed: 10231473
doi: 10.1046/j.1523-1755.1999.00502.x
Zhou Y, Khan H, Xiao J, Cheang WS (2021) Effects of arachidonic acid metabolites on cardiovascular health and disease. Int J Mol Sci 22:12029
pubmed: 34769460
pmcid: 8584625
doi: 10.3390/ijms222112029
Nie D, Honn KV (2002) Cyclooxygenase, lipoxygenase and tumor angiogenesis. Cell Mol Life Sci 59(5):799–807
pubmed: 12088280
pmcid: 11146107
doi: 10.1007/s00018-002-8468-9
Liao Z, Mason KA, Milas L (2007) Cyclo-oxygenase-2 and its inhibition in cancer: is there a role? Drugs 67(6):821–845
pubmed: 17428102
doi: 10.2165/00003495-200767060-00001
Moon H, White AC, Borowsky AD (2020) New insights into the functions of Cox-2 in skin and esophageal malignancies. Exp Mol Med 52(4):538–547
pubmed: 32235869
pmcid: 7210257
doi: 10.1038/s12276-020-0412-2
Brown JR, DuBois RN (2005) COX-2: a molecular target for colorectal cancer prevention. J Clin Oncol 23(12):2840–2855
pubmed: 15837998
doi: 10.1200/JCO.2005.09.051
Nagaraju GP, El-Rayes BF (2019) Cyclooxygenase-2 in gastrointestinal malignancies. Cancer 125(8):1221–1227
pubmed: 30747998
doi: 10.1002/cncr.32010
Hashemi Goradel N, Najafi M, Salehi E, Farhood B, Mortezaee K (2019) Cyclooxygenase-2 in cancer: a review. J Cell Physiol 234(5):5683–5699
pubmed: 30341914
doi: 10.1002/jcp.27411
Li Q, Ma C, Zhang Z, Chen S, Zhi W, Zhang L, Zhang G, Shi L, Cao F, Ma T (2018) Association between cyclooxygenase-2 (COX-2) 8473 T > C polymorphism and cancer risk: a meta-analysis and trial sequential analysis. BMC Cancer 18(1):847
pubmed: 30143023
pmcid: 6109290
doi: 10.1186/s12885-018-4753-3
Harris RE (2009) Cyclooxygenase-2 (cox-2) blockade in the chemoprevention of cancers of the colon, breast, prostate, and lung. Inflammopharmacology 17(2):55–67
pubmed: 19340409
doi: 10.1007/s10787-009-8049-8
Yang X, Xu Y, Wang T, Shu D, Guo P, Miskimins K, Qian SY (2017) Inhibition of cancer migration and invasion by knocking down delta-5-desaturase in COX-2 overexpressed cancer cells. Redox Biol 11:653–62
pubmed: 28157665
pmcid: 5288391
doi: 10.1016/j.redox.2017.01.016
Barker HE, Cox TR, Erler JT (2012) The rationale for targeting the LOX family in cancer. Nat Rev Cancer 12(8):540–552
pubmed: 22810810
doi: 10.1038/nrc3319
Wan M, Tang X, Stsiapanava A, Haeggström JZ (2017) Biosynthesis of leukotriene B(4). Semin Immunol 33:3–15
pubmed: 29042025
doi: 10.1016/j.smim.2017.07.012
Chang J, Tang N, Fang Q, Zhu K, Liu L, Xiong X, Zhu Z, Zhang B, Zhang M, Tao J (2019) Inhibition of COX-2 and 5-LOX regulates the progression of colorectal cancer by promoting PTEN and suppressing PI3K/AKT pathway. Biochem Biophys Res Commun 517(1):1–7
pubmed: 29339153
doi: 10.1016/j.bbrc.2018.01.061
Merchant N, Bhaskar L, Momin S, Sujatha P, Reddy ABM, Nagaraju GP (2018) 5-Lipoxygenase: its involvement in gastrointestinal malignancies. Crit Rev Oncol Hematol 127:50–5
pubmed: 29891111
doi: 10.1016/j.critrevonc.2018.05.012
Zhang B, Wang CL, Zhao WH, Lv M, Wang CY, Zhong WX, Zhou WY, Yu WS, Zhang Y, Li S (2008) Effect of 5-LOX/COX-2 common inhibitor DHDMBF30 on pancreatic cancer cell Capan2. World J Gastroenterol 14(16):2494–2500
pubmed: 18442195
pmcid: 2708359
doi: 10.3748/wjg.14.2494
Ye YN, Wu WK, Shin VY, Bruce IC, Wong BC, Cho CH (2005) Dual inhibition of 5-LOX and COX-2 suppresses colon cancer formation promoted by cigarette smoke. Carcinogenesis 26(4):827–834
pubmed: 15637091
doi: 10.1093/carcin/bgi012
Pidgeon GP, Lysaght J, Krishnamoorthy S, Reynolds JV, O’Byrne K, Nie D, Honn KV (2007) Lipoxygenase metabolism: roles in tumor progression and survival. Cancer Metastasis Rev 26(3–4):503–524
pubmed: 17943411
doi: 10.1007/s10555-007-9098-3
Bécuwe P, Bianchi A, Didelot C, Barberi-Heyob M, Dauça M (2003) Arachidonic acid activates a functional AP-1 and an inactive NF-kappaB complex in human HepG2 hepatoma cells. Free Radic Biol Med 35(6):636–647
pubmed: 12957656
doi: 10.1016/S0891-5849(03)00387-3
Pomianowska E, Schjølberg AR, Clausen OP, Gladhaug IP (2014) COX-2 overexpression in resected pancreatic head adenocarcinomas correlates with favourable prognosis. BMC Cancer 14:458
pubmed: 24950702
pmcid: 4230243
doi: 10.1186/1471-2407-14-458
Knab LM, Grippo PJ, Bentrem DJ (2014) Involvement of eicosanoids in the pathogenesis of pancreatic cancer: the roles of cyclooxygenase-2 and 5-lipoxygenase. World J Gastroenterol 20(31):10729–10739
pubmed: 25152576
pmcid: 4138453
doi: 10.3748/wjg.v20.i31.10729
Alvarez ML, Lorenzetti F (2021) Role of eicosanoids in liver repair, regeneration and cancer. Biochem Pharmacol 192:114732
pubmed: 34411565
doi: 10.1016/j.bcp.2021.114732
Leng J, Han C, Demetris AJ, Michalopoulos GK, Wu T (2003) Cyclooxygenase-2 promotes hepatocellular carcinoma cell growth through Akt activation: evidence for Akt inhibition in celecoxib-induced apoptosis. Hepatology 38(3):756–768
pubmed: 12939602
doi: 10.1053/jhep.2003.50380
Bae SH, Jung ES, Park YM, Kim BS, Kim BK, Kim DG, Ryu WS (2001) Expression of cyclooxygenase-2 (COX-2) in hepatocellular carcinoma and growth inhibition of hepatoma cell lines by a COX-2 inhibitor, NS-398. Clin Cancer Res 7(5):1410–1418
pubmed: 11350912
Dong XF, Liu TQ, Zhi XT, Zou J, Zhong JT, Li T, Mo XL, Zhou W, Guo WW, Liu X et al (2018) COX-2/PGE2 axis regulates HIF2α activity to promote hepatocellular carcinoma hypoxic response and reduce the sensitivity of sorafenib treatment. Clin Cancer Res 24(13):3204–3216
pubmed: 29514844
doi: 10.1158/1078-0432.CCR-17-2725
Sun L, Suo C, Zhang T, Shen S, Gu X, Qiu S, Zhang P, Wei H, Ma W, Yan R et al (2023) ENO1 promotes liver carcinogenesis through YAP1-dependent arachidonic acid metabolism. Nat Chem Biol 19(12):1492–1503
pubmed: 37500770
doi: 10.1038/s41589-023-01391-6
Xu XM, Deng JJ, Yuan GJ, Yang F, Guo HT, Xiang M, Ge W, Wu YG (2011) 5-Lipoxygenase contributes to the progression of hepatocellular carcinoma. Mol Med Rep 4(6):1195–1200
pubmed: 21833474
Wang Q, Zhang WY, Ye LH, Zhang XD (2010) A mutant of HBx (HBxDelta127) promotes hepatoma cell growth via sterol regulatory element binding protein 1c involving 5-lipoxygenase. Acta Pharmacol Sin 31(3):367–374
pubmed: 20173757
pmcid: 4002418
doi: 10.1038/aps.2010.5
Nosaka T, Baba T, Tanabe Y, Sasaki S, Nishimura T, Imamura Y, Yurino H, Hashimoto S, Arita M, Nakamoto Y et al (2018) Alveolar macrophages drive hepatocellular carcinoma lung metastasis by generating leukotriene B(4). J Immunol 200(5):1839–1852
pubmed: 29378914
doi: 10.4049/jimmunol.1700544
Arai J, Goto K, Otoyama Y, Nakajima Y, Sugiura I, Kajiwara A, Tojo M, Ichikawa Y, Uozumi S, Shimozuma Y et al (2021) Leukotriene receptor antagonists enhance HCC treatment efficacy by inhibiting ADAMs and suppressing MICA shedding. Cancer Immunol Immunother 70(1):203–213
pubmed: 32683508
doi: 10.1007/s00262-020-02660-2
Zhang D, Lou J, Zhang X, Zhang L, Wang F, Xu D, Niu N, Wang Y, Wu Y, Cui W (2017) Hyperhomocysteinemia results from and promotes hepatocellular carcinoma via CYP450 metabolism by CYP2J2 DNA methylation. Oncotarget 8(9):15377–15392
pubmed: 28030819
doi: 10.18632/oncotarget.14165
Jeon YJ, Kim JS, Hwang GH, Wu Z, Han HJ, Park SH, Chang W, Kim LK, Lee YM, Liu KH et al (2015) Inhibition of cytochrome P450 2J2 by tanshinone IIA induces apoptotic cell death in hepatocellular carcinoma HepG2 cells. Eur J Pharmacol 764:480–8
pubmed: 26209360
doi: 10.1016/j.ejphar.2015.07.047
Yang F, Zhang Y, Ren H, Wang J, Shang L, Liu Y, Zhu W, Shi X (2019) Ischemia reperfusion injury promotes recurrence of hepatocellular carcinoma in fatty liver via ALOX12-12HETE-GPR31 signaling axis. J Exp Clin Cancer Res 38(1):489
pubmed: 31831037
pmcid: 6909624
doi: 10.1186/s13046-019-1480-9
Wang D, Dubois RN (2010) The role of COX-2 in intestinal inflammation and colorectal cancer. Oncogene 29(6):781–788
pubmed: 19946329
doi: 10.1038/onc.2009.421
Dixon DA, Blanco FF, Bruno A, Patrignani P (2013) Mechanistic aspects of COX-2 expression in colorectal neoplasia. Recent Results Cancer Res 191:7–37
pubmed: 22893198
pmcid: 3477597
doi: 10.1007/978-3-642-30331-9_2
Tuncer S, Banerjee S (2015) Eicosanoid pathway in colorectal cancer: recent updates. World J Gastroenterol 21(41):11748–11766
pubmed: 26557000
pmcid: 4631974
doi: 10.3748/wjg.v21.i41.11748
Liu J, Huang C, Wang J, Huang L, Chen S (2019) COX-2/C-MET/KRAS status-based prognostic nomogram for colorectal cancer: a multicenter cohort study. Saudi J Gastroenterol 25(5):293–301
pubmed: 30720004
pmcid: 6784436
doi: 10.4103/sjg.SJG_502_18
Zhang Z, Ghosh A, Connolly PJ, King P, Wilde T, Wang J, Dong Y, Li X, Liao D, Chen H et al (2021) Gut-restricted selective cyclooxygenase-2 (COX-2) inhibitors for chemoprevention of colorectal cancer. J Med Chem 64(15):11570–11596
pubmed: 34279934
doi: 10.1021/acs.jmedchem.1c00890
Buzharevski A, Paskas S, Sárosi MB, Laube M, Lönnecke P, Neumann W, Mijatovic S, Maksimovic-Ivanic D, Pietzsch J, Hey-Hawkins E (2019) Carboranyl analogues of celecoxib with potent cytostatic activity against human melanoma and colon cancer cell lines. ChemMedChem 14(3):315–321
pubmed: 30602073
doi: 10.1002/cmdc.201800685
Arber N (2008) Cyclooxygenase-2 inhibitors in colorectal cancer prevention: point. Cancer Epidemiol Biomarkers Prev 17(8):1852–1857
pubmed: 18708371
doi: 10.1158/1055-9965.EPI-08-0167
Wang D, Dubois RN (2006) Prostaglandins and cancer Gut 55(1):115–122
pubmed: 16118353
Backlund MG, Mann JR, Dubois RN (2005) Mechanisms for the prevention of gastrointestinal cancer: the role of prostaglandin E2. Oncology 69:28–32
pubmed: 16210874
doi: 10.1159/000086629
Kaidi A, Qualtrough D, Williams AC, Paraskeva C (2006) Direct transcriptional up-regulation of cyclooxygenase-2 by hypoxia-inducible factor (HIF)-1 promotes colorectal tumor cell survival and enhances HIF-1 transcriptional activity during hypoxia. Cancer Res 66(13):6683–6691
pubmed: 16818642
doi: 10.1158/0008-5472.CAN-06-0425
Rodriguez DA, Tapia JC, Fernandez JG, Torres VA, Muñoz N, Galleguillos D, Leyton L, Quest AF (2009) Caveolin-1-mediated suppression of cyclooxygenase-2 via a beta-catenin-Tcf/Lef-dependent transcriptional mechanism reduced prostaglandin E2 production and survivin expression. Mol Biol Cell 20(8):2297–2310
pubmed: 19244345
pmcid: 2669036
doi: 10.1091/mbc.e08-09-0939
Gamez-Belmonte R, Mahapatro M, Erkert L, Gonzalez-Acera M, Naschberger E, Yu Y, Tena-Garitaonaindia M, Patankar JV, Wagner Y, Podstawa E et al (2023) Epithelial presenilin-1 drives colorectal tumour growth by controlling EGFR-COX2 signalling. Gut 72(6):1155–1166
pubmed: 36261293
doi: 10.1136/gutjnl-2022-327323
Castellone MD, Teramoto H, Williams BO, Druey KM, Gutkind JS (2005) Prostaglandin E2 promotes colon cancer cell growth through a Gs-axin-beta-catenin signaling axis. Science 310(5753):1504–1510
pubmed: 16293724
doi: 10.1126/science.1116221
Yaqub S, Henjum K, Mahic M, Jahnsen FL, Aandahl EM, Bjørnbeth BA, Taskén K (2008) Regulatory T cells in colorectal cancer patients suppress anti-tumor immune activity in a COX-2 dependent manner. Cancer Immunol Immunother 57(6):813–821
pubmed: 17962941
doi: 10.1007/s00262-007-0417-x
Melstrom LG, Bentrem DJ, Salabat MR, Kennedy TJ, Ding XZ, Strouch M, Rao SM, Witt RC, Ternent CA, Talamonti MS et al (2008) Overexpression of 5-lipoxygenase in colon polyps and cancer and the effect of 5-LOX inhibitors in vitro and in a murine model. Clin Cancer Res 14(20):6525–6530
pubmed: 18927292
doi: 10.1158/1078-0432.CCR-07-4631
Enayetallah AE, French RA, Grant DF (2006) Distribution of soluble epoxide hydrolase, cytochrome P450 2C8, 2C9 and 2J2 in human malignant neoplasms. J Mol Histol 37(3–4):133–141
pubmed: 16957870
doi: 10.1007/s10735-006-9050-9
Hill R, Li Y, Tran LM, Dry S, Calvopina JH, Garcia A, Kim C, Wang Y, Donahue TR, Herschman HR et al (2012) Cell intrinsic role of COX-2 in pancreatic cancer development. Mol Cancer Ther 11(10):2127–2137
pubmed: 22784710
pmcid: 3469770
doi: 10.1158/1535-7163.MCT-12-0342
Hu H, Han T, Zhuo M, Wu LL, Yuan C, Wu L, Lei W, Jiao F, Wang LW (2017) Elevated COX-2 expression promotes angiogenesis through EGFR/p38-MAPK/Sp1-dependent signalling in pancreatic cancer. Sci Rep 7(1):470
pubmed: 28352075
pmcid: 5428057
doi: 10.1038/s41598-017-00288-4
Gong J, Xie J, Bedolla R, Rivas P, Chakravarthy D, Freeman JW, Reddick R, Kopetz S, Peterson A, Wang H et al (2014) Combined targeting of STAT3/NF-κB/COX-2/EP4 for effective management of pancreatic cancer. Clin Cancer Res 20(5):1259–1273
pubmed: 24520096
pmcid: 3969421
doi: 10.1158/1078-0432.CCR-13-1664
Yoshida S, Ujiki M, Ding XZ, Pelham C, Talamonti MS, Bell RH Jr, Denham W, Adrian TE (2005) Pancreatic stellate cells (PSCs) express cyclooxygenase-2 (COX-2) and pancreatic cancer stimulates COX-2 in PSCs. Mol Cancer. https://doi.org/10.1186/1476-4598-4-27
doi: 10.1186/1476-4598-4-27
pubmed: 16083499
pmcid: 1201567
Zhou GX, Ding XL, Wu SB, Zhang HF, Cao W, Qu LS, Zhang H (2015) Inhibition of 5-lipoxygenase triggers apoptosis in pancreatic cancer cells. Oncol Rep 33(2):661–668
pubmed: 25483364
doi: 10.3892/or.2014.3650
Gregor JI, Kilian M, Heukamp I, Kiewert C, Kristiansen G, Schimke I, Walz MK, Jacobi CA, Wenger FA (2005) Effects of selective COX-2 and 5-LOX inhibition on prostaglandin and leukotriene synthesis in ductal pancreatic cancer in Syrian hamster. Prostaglandins Leukot Essent Fatty Acids 73(2):89–97
pubmed: 15964750
doi: 10.1016/j.plefa.2005.04.016
Zhang A, Zou X, Yang S, Yang H, Ma Z, Li J (2023) Effect of NETs/COX-2 pathway on immune microenvironment and metastasis in gastric cancer. Front Immunol 14:1177604
pubmed: 37153547
pmcid: 10156975
doi: 10.3389/fimmu.2023.1177604
Thiel A, Mrena J, Ristimäki A (2011) Cyclooxygenase-2 and gastric cancer. Cancer Metastasis Rev 30(3–4):387–395
pubmed: 22002749
doi: 10.1007/s10555-011-9312-1
Potter JD, Ulrich CM (2006) COX-2 and gastric cancer: More on inflammation and neoplasia. Gastroenterology 130(7):2198–2200
pubmed: 16762640
doi: 10.1053/j.gastro.2006.04.037
Ye Y, Liu M, Yuan H, Ning S, Wang Y, Chen Z, Ji R, Guo Q, Li Q, Zhou Y (2017) COX-2 regulates Snail expression in gastric cancer via the Notch1 signaling pathway. Int J Mol Med 40(2):512–522
pubmed: 28586004
doi: 10.3892/ijmm.2017.3011
Lim JW, Kim H, Kim KH (2001) Nuclear factor-kappaB regulates cyclooxygenase-2 expression and cell proliferation in human gastric cancer cells. Lab Invest 81(3):349–360
pubmed: 11310828
doi: 10.1038/labinvest.3780243
Lin H, Weng J, Mei H, Zhuang M, Xiao X, Du F, Lin L, Wu J, Chen Z, Huang Y et al (2021) 5-Lipoxygenase promotes epithelial-mesenchymal transition through the ERK signaling pathway in gastric cancer. J Gastroenterol Hepatol 36(2):455–466
pubmed: 32667711
doi: 10.1111/jgh.15184
Tian YQ, Liu J, Cheng P, Zou J, Xu HF, Shi XH, Zhang YS, Mei L (2023) Dual COX-2/5-LOX inhibitors from zanthoxylum simulans inhibit gastric cancer cells by cross-mediating thyroid, estrogen, and oxytocin signaling pathways. Front Chem 11:1287570
pubmed: 38268762
doi: 10.3389/fchem.2023.1287570
Hu Z, Yang Y, Zhao Y, Huang Y (2017) The prognostic value of cyclooxygenase-2 expression in patients with esophageal cancer: evidence from a meta-analysis. Onco Targets Ther 10:2893–901
pubmed: 28652771
pmcid: 5476766
doi: 10.2147/OTT.S134599
Chen J, Wu F, Pei HL, Gu WD, Ning ZH, Shao YJ, Huang J (2015) Analysis of the correlation between P53 and Cox-2 expression and prognosis in esophageal cancer. Oncol Lett 10(4):2197–2203
pubmed: 26622818
pmcid: 4579898
doi: 10.3892/ol.2015.3624
Lin Y, Shen LY, Fu H, Dong B, Yang HL, Yan WP, Kang XZ, Dai L, Zhou HT, Yang YB et al (2017) P21, COX-2, and E-cadherin are potential prognostic factors for esophageal squamous cell carcinoma. Dis Esophagus 30(2):1–10
pubmed: 28859386
Zhi H, Wang L, Zhang J, Zhou C, Ding F, Luo A, Wu M, Zhan Q, Liu Z (2006) Significance of COX-2 expression in human esophageal squamous cell carcinoma. Carcinogenesis 27(6):1214–1221
pubmed: 16352617
doi: 10.1093/carcin/bgi304
Pun IH, Chan D, Chan SH, Chung PY, Zhou YY, Law S, Lam AK, Chui CH, Chan AS, Lam KH et al (2017) Anti-cancer Effects of a novel quinoline derivative 83b1 on human esophageal squamous cell carcinoma through down-regulation of COX-2 mRNA and PGE(2). Cancer Res Treat 49(1):219–229
pubmed: 27456944
doi: 10.4143/crt.2016.190
Corley DA, Kerlikowske K, Verma R, Buffler P (2003) Protective association of aspirin/NSAIDs and esophageal cancer: a systematic review and meta-analysis. Gastroenterology 124(1):47–56
pubmed: 12512029
doi: 10.1053/gast.2003.50008
Chen X, Wang S, Wu N, Sood S, Wang P, Jin Z, Beer DG, Giordano TJ, Lin Y, Shih WC et al (2004) Overexpression of 5-lipoxygenase in rat and human esophageal adenocarcinoma and inhibitory effects of zileuton and celecoxib on carcinogenesis. Clin Cancer Res 10(19):6703–6709
pubmed: 15475461
doi: 10.1158/1078-0432.CCR-04-0838
Hoque A, Lippman SM, Wu TT, Xu Y, Liang ZD, Swisher S, Zhang H, Cao L, Ajani JA, Xu XC (2005) Increased 5-lipoxygenase expression and induction of apoptosis by its inhibitors in esophageal cancer: a potential target for prevention. Carcinogenesis 26(4):785–791
pubmed: 15661803
doi: 10.1093/carcin/bgi026
Shi HY, Lv FJ, Zhu ST, Wang QG, Zhang ST (2011) Dual inhibition of 5-LOX and COX-2 suppresses esophageal squamous cell carcinoma. Cancer Lett 309(1):19–26
pubmed: 21652147
doi: 10.1016/j.canlet.2011.05.010
Legan M (2010) Cyclooxygenase-2, p53 and glucose transporter-1 as predictors of malignancy in the development of gallbladder carcinomas. Bosn J Basic Med Sci 10(3):192–196
pubmed: 20846124
pmcid: 5504494
doi: 10.17305/bjbms.2010.2684
Longo WE, Panesar N, Mazuski JE, Kaminski D (1999) Synthetic pathways of gallbladder mucosal prostanoids: the role of cyclooxygenase-1 and 2. Prostaglandins Leukot Essent Fatty Acids 60(2):77–85
pubmed: 10328326
doi: 10.1054/plef.1999.0011
Legan M, Luzar B, Marolt VF, Cor A (2006) Expression of cyclooxygenase-2 is associated with p53 accumulation in premalignant and malignant gallbladder lesions. World J Gastroenterol 12(21):3425–3429
pubmed: 16733863
pmcid: 4087877
doi: 10.3748/wjg.v12.i21.3425
Zhi YH, Liu RS, Song MM, Tian Y, Long J, Tu W, Guo RX (2005) Cyclooxygenase-2 promotes angiogenesis by increasing vascular endothelial growth factor and predicts prognosis in gallbladder carcinoma. World J Gastroenterol 11(24):3724–3728
pubmed: 15968728
pmcid: 4316024
doi: 10.3748/wjg.v11.i24.3724
Asano T, Shoda J, Ueda T, Kawamoto T, Todoroki T, Shimonishi M, Tanabe T, Sugimoto Y, Ichikawa A, Mutoh M et al (2002) Expressions of cyclooxygenase-2 and prostaglandin E-receptors in carcinoma of the gallbladder: crucial role of arachidonate metabolism in tumor growth and progression. Clin Cancer Res 8(4):1157–1167
pubmed: 11948128
Moon WS, Park HS, Lee H, Pai R, Tarnawski AS, Kim KR, Jang KY (2005) Co-expression of cox-2, C-met and beta-catenin in cells forming invasive front of gallbladder cancer. Cancer Res Treat 37(3):171–176
pubmed: 19956499
pmcid: 2785404
doi: 10.4143/crt.2005.37.3.171
Kawamoto T, Shoda J, Asano T, Ueda T, Furukawa M, Koike N, Tanaka N, Todoroki T, Miwa M (2002) Expression of cyclooxygenase-2 in the subserosal layer correlates with postsurgical prognosis of pathological tumor stage 2 carcinoma of the gallbladder. Int J Cancer 98(3):427–434
pubmed: 11920595
doi: 10.1002/ijc.10222
Nemunaitis JM, Brown-Glabeman U, Soares H, Belmonte J, Liem B, Nir I, Phuoc V, Gullapalli RR (2018) Gallbladder cancer: review of a rare orphan gastrointestinal cancer with a focus on populations of New Mexico. BMC Cancer 18(1):665
pubmed: 29914418
pmcid: 6006713
doi: 10.1186/s12885-018-4575-3
Lazcano-Ponce EC, Miquel JF, Muñoz N, Herrero R, Ferrecio C, Wistuba II, Alonso de Ruiz P, Aristi Urista G, Nervi F (2001) Epidemiology and molecular pathology of gallbladder cancer. CA Cancer J Clin 51(6):349–364
pubmed: 11760569
doi: 10.3322/canjclin.51.6.349
Roa JC, García P, Kapoor VK, Maithel SK, Javle M, Koshiol J (2022) Gallbladder cancer Nat Rev Dis Primers 8(1):69
pubmed: 36302789
doi: 10.1038/s41572-022-00398-y
Sharma P, Caldwell TS, Rivera MN, Gullapalli RR (2020) Cadmium exposure activates Akt/ERK signaling and pro-inflammatory COX-2 expression in human gallbladder epithelial cells via a ROS dependent mechanism. Toxicol In Vitro 67:104912
pubmed: 32512147
pmcid: 7809918
doi: 10.1016/j.tiv.2020.104912
Malik IA (2004) Gallbladder cancer: current status. Expert Opin Pharmacother 5(6):1271–1277
pubmed: 15163272
doi: 10.1517/14656566.5.6.1271
Kiguchi K, Ruffino L, Kawamoto T, Franco E, Kurakata S, Fujiwara K, Hanai M, Rumi M, DiGiovanni J (2007) Therapeutic effect of CS-706, a specific cyclooxygenase-2 inhibitor, on gallbladder carcinoma in BK5.ErbB-2 mice. Mol Cancer Ther 6:1709–17
pubmed: 17575102
doi: 10.1158/1535-7163.MCT-07-0015
Deng M, Qin Y, Chen X, Li D, Wang Q, Zheng H, Gu L, Deng C, Xue Y, Zhu D et al (2017) Combination of celecoxib and PD184161 exerts synergistic inhibitory effects on gallbladder cancer cell proliferation. Oncol Lett 13(5):3850–3858
pubmed: 28521485
pmcid: 5431146
doi: 10.3892/ol.2017.5914
Zhang C, Liu X, Jin S, Chen Y, Guo R (2022) Ferroptosis in cancer therapy: a novel approach to reversing drug resistance. Mol Cancer 21(1):47
pubmed: 35151318
pmcid: 8840702
doi: 10.1186/s12943-022-01530-y
Li D, Wang Y, Dong C, Chen T, Dong A, Ren J, Li W, Shu G, Yang J, Shen W et al (2023) CST1 inhibits ferroptosis and promotes gastric cancer metastasis by regulating GPX4 protein stability via OTUB1. Oncogene 42(2):83–98
pubmed: 36369321
doi: 10.1038/s41388-022-02537-x
Mou Y, Wang J, Wu J, He D, Zhang C, Duan C, Li B (2019) Ferroptosis, a new form of cell death: opportunities and challenges in cancer. J Hematol Oncol 12(1):34
pubmed: 30925886
pmcid: 6441206
doi: 10.1186/s13045-019-0720-y
Chen X, Kang R, Kroemer G, Tang D (2021) Broadening horizons: the role of ferroptosis in cancer. Nat Rev Clin Oncol 18(5):280–296
pubmed: 33514910
doi: 10.1038/s41571-020-00462-0
Huang Y, Wang S, Ke A (1878) Guo K (2023) Ferroptosis and its interaction with tumor immune microenvironment in liver cancer. Biochim Biophys Acta Rev Cancer 1:188848
Wang Z, Zhou C, Zhang Y, Tian X, Wang H, Wu J, Jiang S (2024) From synergy to resistance: Navigating the complex relationship between sorafenib and ferroptosis in hepatocellular carcinoma. Biomed Pharmacother 170:116074
pubmed: 38147732
doi: 10.1016/j.biopha.2023.116074
Zhang X, Chen Y, Li X, Xu H, Yang J, Wang C, Zhang C, Deng Y, Lu A, Zheng C et al (2024) Carrier-free self-assembled nanomedicine based on celastrol and galactose for targeting therapy of hepatocellular carcinoma via inducing ferroptosis. Eur J Med Chem 267:116183
pubmed: 38354520
doi: 10.1016/j.ejmech.2024.116183
Tian H, Zhao S, Nice EC, Huang C, He W, Zou B, Lin J (2022) A cascaded copper-based nanocatalyst by modulating glutathione and cyclooxygenase-2 for hepatocellular carcinoma therapy. J Colloid Interface Sci 607(Pt 2):1516–1526
pubmed: 34592546
doi: 10.1016/j.jcis.2021.09.049
Yang Y, Liu C, Wang M, Cheng H, Wu H, Luo S, Zhang M, Duan X, Li Q (2024) Arenobufagin regulates the p62-Keap1-Nrf2 pathway to induce autophagy-dependent ferroptosis in HepG2 cells. Naunyn Schmiedebergs Arch Pharmacol 397(7):4895–4909
pubmed: 38165425
doi: 10.1007/s00210-023-02916-5
Hassannia B, Vandenabeele P, Vanden Berghe T (2019) Targeting Ferroptosis to Iron Out Cancer. Cancer Cell 35(6):830–849
pubmed: 31105042
doi: 10.1016/j.ccell.2019.04.002
Liang C, Zhang X, Yang M, Dong X (2019) Recent Progress in Ferroptosis Inducers for Cancer Therapy. Adv Mater 31(51):e1904197
pubmed: 31595562
doi: 10.1002/adma.201904197
Tong X, Tang R, Xiao M, Xu J, Wang W, Zhang B, Liu J, Yu X, Shi S (2022) Targeting cell death pathways for cancer therapy: recent developments in necroptosis, pyroptosis, ferroptosis, and cuproptosis research. J Hematol Oncol 15(1):174
pubmed: 36482419
pmcid: 9733270
doi: 10.1186/s13045-022-01392-3
Marks F, Fürstenberger G, Müller-Decker K (1998) Arachidonic acid metabolism as a reporter of skin irritancy and target of cancer chemoprevention. Toxicol Lett 96–97:111–8
pubmed: 9820655
doi: 10.1016/S0378-4274(98)00057-5
Chan AT, Ogino S, Fuchs CS (2007) Aspirin and the risk of colorectal cancer in relation to the expression of COX-2. N Engl J Med 356(21):2131–2142
pubmed: 17522398
doi: 10.1056/NEJMoa067208
Markowitz SD (2007) Aspirin and colon cancer–targeting prevention? N Engl J Med 356(21):2195–2198
pubmed: 17522404
doi: 10.1056/NEJMe078044
Gautam S, Roy S, Ansari MN, Saeedan AS, Saraf SA, Kaithwas G (2017) DuCLOX-2/5 inhibition: a promising target for cancer chemoprevention. Breast Cancer 24(2):180–190
pubmed: 27558792
doi: 10.1007/s12282-016-0723-2
El-Miligy MMM, Al-Kubeisi AK, El-Zemity SR, Nassra RA, Abu-Serie MM, Hazzaa AA (2021) Discovery of small molecule acting as multitarget inhibitor of colorectal cancer by simultaneous blocking of the key COX-2, 5-LOX and PIM-1 kinase enzymes. Bioorg Chem 115:105171
pubmed: 34303896
doi: 10.1016/j.bioorg.2021.105171
Bishayee K, Khuda-Bukhsh AR (2013) 5-lipoxygenase antagonist therapy: a new approach towards targeted cancer chemotherapy. Acta Biochim Biophys Sin (Shanghai) 45(9):709–719
pubmed: 23752617
doi: 10.1093/abbs/gmt064
Vishnupriya P, Aparna A, Viswanadha VP (2021) Lipoxygenase (LOX) Pathway: a promising target to combat cancer. Curr Pharm Des 27(31):3349–3369
pubmed: 33388012
doi: 10.2174/1381612826666210101153216
Aparoy P, Reddy KK, Reddanna P (2012) Structure and ligand based drug design strategies in the development of novel 5- LOX inhibitors. Curr Med Chem 19(22):3763–3778
pubmed: 22680930
pmcid: 3480706
doi: 10.2174/092986712801661112
Ding X, Zhu C, Qiang H, Zhou X, Zhou G (2011) Enhancing antitumor effects in pancreatic cancer cells by combined use of COX-2 and 5-LOX inhibitors. Biomed Pharmacother 65(7):486–490
pubmed: 21993002
doi: 10.1016/j.biopha.2011.06.009
Tavolari S, Bonafè M, Marini M, Ferreri C, Bartolini G, Brighenti E, Manara S, Tomasi V, Laufer S, Guarnieri T (2008) Licofelone, a dual COX/5-LOX inhibitor, induces apoptosis in HCA-7 colon cancer cells through the mitochondrial pathway independently from its ability to affect the arachidonic acid cascade. Carcinogenesis 29(2):371–380
pubmed: 18033773
doi: 10.1093/carcin/bgm265
Leval X, Julemont F, Delarge J, Pirotte B, Dogne JM (2002) New trends in dual 5-LOX/COX inhibition. Curr Med Chem 9(9):941–962
pubmed: 11966455
doi: 10.2174/0929867024606713
Panigrahy D, Kaipainen A, Greene ER, Huang S (2010) Cytochrome P450-derived eicosanoids: the neglected pathway in cancer. Cancer Metastasis Rev 29(4):723–735
pubmed: 20941528
pmcid: 2962793
doi: 10.1007/s10555-010-9264-x
Zordoky BN, El-Kadi AO (2010) Effect of cytochrome P450 polymorphism on arachidonic acid metabolism and their impact on cardiovascular diseases. Pharmacol Ther 125(3):446–463
pubmed: 20093140
doi: 10.1016/j.pharmthera.2009.12.002
Sobolewski C, Legrand N (2021) Celecoxib analogues for cancer treatment: an update on OSU-03012 and 2,5-Dimethyl-celecoxib. Biomolecules 11:1049
pubmed: 34356673
pmcid: 8302000
doi: 10.3390/biom11071049
Yarla NS, Bishayee A, Sethi G, Reddanna P, Kalle AM, Dhananjaya BL, Dowluru KS, Chintala R, Duddukuri GR (2016) Targeting arachidonic acid pathway by natural products for cancer prevention and therapy. Semin Cancer Biol 40–41:48–81
pubmed: 26853158
doi: 10.1016/j.semcancer.2016.02.001
Li S, Jiang M, Wang L, Yu S (2020) Combined chemotherapy with cyclooxygenase-2 (COX-2) inhibitors in treating human cancers: Recent advancement. Biomed Pharmacother 129:110389
pubmed: 32540642
doi: 10.1016/j.biopha.2020.110389
Menter DG, Schilsky RL, DuBois RN (2010) Cyclooxygenase-2 and cancer treatment: understanding the risk should be worth the reward. Clin Cancer Res 16(5):1384–1390
pubmed: 20179228
pmcid: 4307592
doi: 10.1158/1078-0432.CCR-09-0788
Cao Y, Nishihara R, Qian ZR, Song M, Mima K, Inamura K, Nowak JA, Drew DA, Lochhead P, Nosho K et al (2016) Regular aspirin use associates with lower risk of colorectal cancers with low numbers of tumor-infiltrating lymphocytes. Gastroenterology 151(5):879–92.e4
pubmed: 27475305
doi: 10.1053/j.gastro.2016.07.030
Gomes RN, Felipe da Costa S, Colquhoun A (2018) Eicosanoids and cancer. Clinics (Sao Paulo) 73(suppl 1):e530s
pubmed: 30133566
doi: 10.6061/clinics/2018/e530s