Role of APE1 in hepatocellular carcinoma and its prospects as a target in clinical settings (Review)
- Authors:
- Lei Yang
- Zhipeng Sun
-
Affiliations: Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, P.R. China - Published online on: September 6, 2024 https://doi.org/10.3892/mco.2024.2780
- Article Number: 82
-
Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
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|
Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A and Bray F: Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 71:209–249. 2021.PubMed/NCBI View Article : Google Scholar | |
|
Singal AG, Kanwal F and Llovet JM: Global trends in hepatocellular carcinoma epidemiology: Implications for screening, prevention and therapy. Nat Rev Clin Oncol. 20:864–884. 2023.PubMed/NCBI View Article : Google Scholar | |
|
Yang JD, Hainaut P, Gores GJ, Amadou A, Plymoth A and Roberts LR: A global view of hepatocellular carcinoma: Trends, risk, prevention and management. Nat Rev Gastroenterol Hepatol. 16:589–604. 2019.PubMed/NCBI View Article : Google Scholar | |
|
Clark T, Maximin S, Meier J, Pokharel S and Bhargava P: Hepatocellular carcinoma: Review of epidemiology, screening, imaging diagnosis, response assessment, and treatment. Curr Probl Diagn Radiol. 44:479–486. 2015.PubMed/NCBI View Article : Google Scholar | |
|
Sia D, Villanueva A, Friedman SL and Llovet JM: Liver cancer cell of origin, molecular class, and effects on patient prognosis. Gastroenterology. 152:745–761. 2017.PubMed/NCBI View Article : Google Scholar | |
|
Zhang H, Su X, Burley SK and Zheng XFS: mTOR regulates aerobic glycolysis through NEAT1 and nuclear paraspeckle-mediated mechanism in hepatocellular carcinoma. Theranostics. 12:3518–3533. 2022.PubMed/NCBI View Article : Google Scholar | |
|
Vogel A, Meyer T, Sapisochin G, Salem R and Saborowski A: Hepatocellular carcinoma. Lancet. 400:1345–1362. 2022.PubMed/NCBI View Article : Google Scholar | |
|
Chang Y, Jeong SW, Young Jang J and Jae Kim Y: Recent updates of transarterial chemoembolilzation in hepatocellular carcinoma. Int J Mol Sci. 21(8165)2020.PubMed/NCBI View Article : Google Scholar | |
|
Galle PP, Dufour JF, Peck-Radosavljevic M, Trojan J and Vogel A: Systemic therapy of advanced hepatocellular carcinoma. Future Oncol. 17:1237–1251. 2021.PubMed/NCBI View Article : Google Scholar | |
|
Llovet JM, De Baere T, Kulik L, Haber PK, Greten TF, Meyer T and Lencioni R: Locoregional therapies in the era of molecular and immune treatments for hepatocellular carcinoma. Nat Rev Gastroenterol Hepatol. 18:293–313. 2021.PubMed/NCBI View Article : Google Scholar | |
|
Llovet JM, Montal R, Sia D and Finn RS: Molecular therapies and precision medicine for hepatocellular carcinoma. Nat Rev Clin Oncol. 15:599–616. 2018.PubMed/NCBI View Article : Google Scholar | |
|
Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, Luo R, Feng J, Ye S, Yang TS, et al: Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: A phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol. 10:25–34. 2009.PubMed/NCBI View Article : Google Scholar | |
|
Llovet JM, Castet F, Heikenwalder M, Maini MK, Mazzaferro V, Pinato DJ, Pikarsky E, Zhu AX and Finn RS: Immunotherapies for hepatocellular carcinoma. Nat Rev Clin Oncol. 19:151–172. 2022.PubMed/NCBI View Article : Google Scholar | |
|
Kong FH, Ye QF, Miao XY, Liu X, Huang SQ, Xiong L, Wen Y and Zhang ZJ: Current status of sorafenib nanoparticle delivery systems in the treatment of hepatocellular carcinoma. Theranostics. 11:5464–5490. 2021.PubMed/NCBI View Article : Google Scholar | |
|
Ladd AD, Duarte S, Sahin I and Zarrinpar A: Mechanisms of drug resistance in HCC. Hepatology. 79:926–940. 2024.PubMed/NCBI View Article : Google Scholar | |
|
Dattachoudhury S, Sharma R, Kumar A and Jaganathan BG: Sorafenib inhibits proliferation, migration and invasion of breast cancer cells. Oncology. 98:478–486. 2020.PubMed/NCBI View Article : Google Scholar | |
|
Tang W, Chen Z, Zhang W, Cheng Y, Zhang B, Wu F, Wang Q, Wang S, Rong D, Reiter FP, et al: The mechanisms of sorafenib resistance in hepatocellular carcinoma: Theoretical basis and therapeutic aspects. Signal Transduct Target Ther. 5(87)2020.PubMed/NCBI View Article : Google Scholar | |
|
Tian C, Liu Y, Xue L, Zhang D, Zhang X, Su J, Chen J, Li X, Wang L and Jiao S: Sorafenib inhibits ovarian cancer cell proliferation and mobility and induces radiosensitivity by targeting the tumor cell epithelial-mesenchymal transition. Open Life Sci. 17:616–625. 2022.PubMed/NCBI View Article : Google Scholar | |
|
Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, de Oliveira AC, Santoro A, Raoul JL, Forner A, et al: Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 359:378–390. 2008.PubMed/NCBI View Article : Google Scholar | |
|
Gupta N, Verma RK, Prinja S and Dhiman RK: Cost-effectiveness of sorafenib for treatment of advanced hepatocellular carcinoma in India. J Clin Exp Hepatol. 9:468–475. 2019.PubMed/NCBI View Article : Google Scholar | |
|
Zschäbitz S and Grüllich C: Lenvantinib: A tyrosine kinase inhibitor of VEGFR 1-3, FGFR 1-4, PDGFRα, KIT and RET. Recent Results Cancer Res. 211:187–198. 2018.PubMed/NCBI View Article : Google Scholar | |
|
Bo W and Chen Y: Lenvatinib resistance mechanism and potential ways to conquer. Front Pharmacol. 14(1153991)2023.PubMed/NCBI View Article : Google Scholar | |
|
Liu X, Lu Y and Qin S: Atezolizumab and bevacizumab for hepatocellular carcinoma: Mechanism, pharmacokinetics and future treatment strategies. Future Oncol. 17:2243–2256. 2021.PubMed/NCBI View Article : Google Scholar | |
|
Gao X, Zhao R, Ma H and Zuo S: Efficacy and safety of atezolizumab plus bevacizumab treatment for advanced hepatocellular carcinoma in the real world: A single-arm meta-analysis. BMC Cancer. 23(635)2023.PubMed/NCBI View Article : Google Scholar | |
|
López DJ, Rodríguez JA and Bañuelos S: Molecular mechanisms regulating the DNA repair protein APE1: A focus on its flexible N-terminal tail domain. Int J Mol Sci. 22(6308)2021.PubMed/NCBI View Article : Google Scholar | |
|
Caston RA, Gampala S, Armstrong L, Messmann RA, Fishel ML and Kelley MR: The multifunctional APE1 DNA repair-redox signaling protein as a drug target in human disease. Drug Discov Today. 26:218–228. 2021.PubMed/NCBI View Article : Google Scholar | |
|
He H, Liu X, Wu Y, Qi L, Huang J, Zhou Y, Zeng J, Wang K and He X: DNA nanotechnology-empowered fluorescence imaging of APE1 Activity. Chemistry. 5:1815–1831. 2023. | |
|
An SY, Jin SA, Seo HJ, Lee YR, Kim S, Jeon BH and Jeong JO: Protective effect of secretory APE1/Ref-1 on doxorubicin-induced cardiotoxicity via suppression of ROS and p53 pathway. ESC Heart Fail. 11:1182–1193. 2024.PubMed/NCBI View Article : Google Scholar | |
|
Zhang S, He L, Dai N, Guan W, Shan J, Yang X, Zhong Z, Qing Y, Jin F, Chen C, et al: Serum APE1 as a predictive marker for platinum-based chemotherapy of non-small cell lung cancer patients. Oncotarget. 7:77482–77494. 2016.PubMed/NCBI View Article : Google Scholar | |
|
McIlwain DW, Fishel ML, Boos A, Kelley MR and Jerde TJ: APE1/Ref-1 redox-specific inhibition decreases survivin protein levels and induces cell cycle arrest in prostate cancer cells. Oncotarget. 9:10962–10977. 2018.PubMed/NCBI View Article : Google Scholar | |
|
Lee YR, Park MS, Joo HK, Kim KM, Kim J, Jeon BH and Choi S: Therapeutic positioning of secretory acetylated APE1/Ref-1 requirement for suppression of tumor growth in triple-negative breast cancer in vivo. Sci Rep. 8(8701)2018.PubMed/NCBI View Article : Google Scholar | |
|
Di Maso V, Mediavilla MG, Vascotto C, Lupo F, Baccarani U, Avellini C, Tell G, Tiribelli C and Crocè LS: Transcriptional Up-Regulation of APE1/Ref-1 in hepatic tumor: Role in hepatocytes resistance to oxidative stress and apoptosis. PLoS One. 10(e0143289)2015.PubMed/NCBI View Article : Google Scholar | |
|
Logsdon DP, Grimard M, Luo M, Shahda S, Jiang Y, Tong Y, Yu Z, Zyromski N, Schipani E, Carta F, et al: Regulation of HIF1α under Hypoxia by APE1/Ref-1 Impacts CA9 expression: Dual targeting in patient-derived 3D pancreatic cancer models. Mol Cancer Ther. 15:2722–2732. 2016.PubMed/NCBI View Article : Google Scholar | |
|
Sun Z, Zhu Y, Aminbuhe Fan Q, Peng J and Zhang N: Differential expression of APE1 in hepatocellular carcinoma and the effects on proliferation and apoptosis of cancer cells. Biosci Trends. 12:456–462. 2018.PubMed/NCBI View Article : Google Scholar | |
|
Lu X, Zhao H, Yuan H, Chu Y and Zhu X: High nuclear expression of APE1 correlates with unfavorable prognosis and promotes tumor growth in hepatocellular carcinoma. J Mol Histol. 52:219–231. 2021.PubMed/NCBI View Article : Google Scholar | |
|
Di Maso V, Avellini C, Crocè LS, Rosso N, Quadrifoglio F, Cesaratto L, Codarin E, Bedogni G, Beltrami CA, Tell G and Tiribelli C: Subcellular localization of APE1/Ref-1 in human hepatocellular carcinoma: Possible prognostic significance. Mol Med. 13:89–96. 2007.PubMed/NCBI View Article : Google Scholar | |
|
Hegde ML, Hazra TK and Mitra S: Early steps in the DNA base excision/single-strand interruption repair pathway in mammalian cells. Cell Res. 18:27–47. 2008.PubMed/NCBI View Article : Google Scholar | |
|
Demple B, Herman T and Chen DS: Cloning and expression of APE, the cDNA encoding the major human apurinic endonuclease: Definition of a family of DNA repair enzymes. Proc Natl Acad Sci U S A. 88:11450–11454. 1991.PubMed/NCBI View Article : Google Scholar | |
|
Kciuk M, Marciniak B, Mojzych M and Kontek R: Focus on UV-Induced DNA damage and repair-disease relevance and protective strategies. Int J Mol Sci. 21(7264)2020.PubMed/NCBI View Article : Google Scholar | |
|
Krokan HE and Bjørås M: Base excision repair. Cold Spring Harb Perspect Biol. 5(a012583)2013.PubMed/NCBI View Article : Google Scholar | |
|
Hindi NN, Elsakrmy N and Ramotar D: The base excision repair process: Comparison between higher and lower eukaryotes. Cell Mol Life Sci. 78:7943–7965. 2021.PubMed/NCBI View Article : Google Scholar | |
|
Khodyreva SN, Prasad R, Ilina ES, Sukhanova MV, Kutuzov MM, Liu Y, Hou EW, Wilson SH and Lavrik OI: Apurinic/apyrimidinic (AP) site recognition by the 5'-dRP/AP lyase in poly(ADP-ribose) polymerase-1 (PARP-1). Proc Natl Acad Sci USA. 107:22090–22095. 2010.PubMed/NCBI View Article : Google Scholar | |
|
Vidal AE, Boiteux S, Hickson ID and Radicella JP: XRCC1 coordinates the initial and late stages of DNA abasic site repair through protein–protein interactions. EMBO J. 20(6530-6539-6539)2001.PubMed/NCBI View Article : Google Scholar | |
|
Bennett RA, Wilson DM III, Wong D and Demple B: Interaction of human apurinic endonuclease and DNA polymerase beta in the base excision repair pathway. Proc Natl Acad Sci USA. 94:7166–7169. 1997.PubMed/NCBI View Article : Google Scholar | |
|
Antoniali G, Serra F, Lirussi L, Tanaka M, D'Ambrosio C, Zhang S, Radovic S, Dalla E, Ciani Y, Scaloni A, et al: Mammalian APE1 controls miRNA processing and its interactome is linked to cancer RNA metabolism. Nat Commun. 8(797)2017.PubMed/NCBI View Article : Google Scholar | |
|
Berquist BR, McNeill DR and Wilson DM III: Characterization of abasic endonuclease activity of human Ape1 on alternative substrates, as well as effects of ATP and sequence context on AP site incision. J Mol Biol. 379:17–27. 2008.PubMed/NCBI View Article : Google Scholar | |
|
Antoniali G, Dalla E, Mangiapane G, Zhao X, Jing X, Cheng Y, De Sanctis V, Ayyildiz D, Piazza S, Li M and Tell G: APE1 controls DICER1 expression in NSCLC through miR-33a and miR-130b. Cell Mol Life Sci. 79(446)2022.PubMed/NCBI View Article : Google Scholar | |
|
Malfatti MC, Antoniali G, Codrich M and Tell G: Coping with RNA damage with a focus on APE1, a BER enzyme at the crossroad between DNA damage repair and RNA processing/decay. DNA Repair (Amst). 104(103133)2021.PubMed/NCBI View Article : Google Scholar | |
|
Kladova OA, Bazlekowa-Karaban M, Baconnais S, Piétrement O, Ishchenko AA, Matkarimov BT, Iakovlev DA, Vasenko A, Fedorova OS, Le Cam E, et al: The role of the N-terminal domain of human apurinic/apyrimidinic endonuclease 1, APE1, in DNA glycosylase stimulation. DNA Repair (Amst). 64:10–25. 2018.PubMed/NCBI View Article : Google Scholar | |
|
Oliveira TT, Coutinho LG, de Oliveira LOA, Timoteo ARS, Farias GC and Agnez-Lima LF: APE1/Ref-1 role in inflammation and immune response. Front Immunol. 13(793096)2022.PubMed/NCBI View Article : Google Scholar | |
|
Hu Z, Hui B, Hou X, Liu R, Sukhanov S and Liu X: APE1 inhibits foam cell formation from macrophages via LOX1 suppression. Am J Transl Res. 12:6559–6568. 2020.PubMed/NCBI | |
|
Luo M, Zhang J, He H, Su D, Chen Q, Gross ML, Kelley MR and Georgiadis MM: Characterization of the Redox activity and disulfide bond formation in apurinic/apyrimidinic endonuclease. Biochemistry. 51:695–705. 2012.PubMed/NCBI View Article : Google Scholar | |
|
Pekhale K, Haval G, Perween N, Antoniali G, Tell G and Ghaskadbi S and Ghaskadbi S: DNA repair enzyme APE1 from evolutionarily ancient Hydra reveals redox activity exclusively found in mammalian APE1. DNA Repair (Amst). 59:44–56. 2017.PubMed/NCBI View Article : Google Scholar | |
|
Kelley MR, Logsdon D and Fishel ML: Targeting DNA repair pathways for cancer treatment: What's new? Future Oncol. 10:1215–1237. 2014.PubMed/NCBI View Article : Google Scholar | |
|
Kelley MR, Georgiadis MM and Fishel ML: APE1/Ref-1 role in redox signaling: Translational applications of targeting the redox function of the DNA repair/redox protein APE1/Ref-1. Curr Mol Pharmacol. 5:36–53. 2012.PubMed/NCBI View Article : Google Scholar | |
|
Georgiadis MM, Luo M, Gaur RK, Delaplane S, Li X and Kelley MR: Evolution of the redox function in mammalian Apurinic/apyrimidinic endonuclease. Mutat Res. 643:54–63. 2008.PubMed/NCBI View Article : Google Scholar | |
|
Lee EO, Joo HK, Lee YR, Kim S, Lee KH, Lee SD and Jeon BH: APE1/Ref-1 inhibits adipogenic transcription factors during adipocyte differentiation in 3T3-L1 cells. Int J Mol Sci. 24(3251)2023.PubMed/NCBI View Article : Google Scholar | |
|
Shah F, Logsdon D, Messmann RA, Fehrenbacher JC, Fishel ML and Kelley MR: Exploiting the Ref-1-APE1 node in cancer signaling and other diseases: From bench to clinic. NPJ Precis Oncol. 1(19)2017.PubMed/NCBI View Article : Google Scholar | |
|
Garcia-Bailo B, El-Sohemy A, Haddad PS, Arora P, Benzaied F, Karmali M and Badawi A: Vitamins D, C, and E in the prevention of type 2 diabetes mellitus: Modulation of inflammation and oxidative stress. Biologics. 5:7–19. 2011.PubMed/NCBI View Article : Google Scholar | |
|
Biswas A, Khanna S, Roy S, Pan X, Sen CK and Gordillo GM: Endothelial cell tumor growth is Ape/ref-1 dependent. Am J Physiol Cell Physiol. 309:C296–C307. 2015.PubMed/NCBI View Article : Google Scholar | |
|
Ding J, Fishel ML, Reed AM, McAdams E, Czader MB, Cardoso AA and Kelley MR: Ref-1/APE1 as a transcriptional regulator and novel therapeutic target in pediatric T-cell Leukemia. Mol Cancer Ther. 16:1401–1411. 2017.PubMed/NCBI View Article : Google Scholar | |
|
Fishel ML, Jiang Y, Rajeshkumar NV, Scandura G, Sinn AL, He Y, Shen C, Jones DR, Pollok KE, Ivan M, et al: Impact of APE1/Ref-1 redox inhibition on pancreatic tumor growth. Mol Cancer Ther. 10:1698–1708. 2011.PubMed/NCBI View Article : Google Scholar | |
|
Vasko MR, Guo C, Thompson EL and Kelley MR: The repair function of the multifunctional DNA repair/redox protein APE1 is neuroprotective after ionizing radiation. DNA Repair (Amst). 10:942–952. 2011.PubMed/NCBI View Article : Google Scholar | |
|
Zou GM and Maitra A: Small-molecule inhibitor of the AP endonuclease 1/REF-1 E3330 inhibits pancreatic cancer cell growth and migration. Mol Cancer Ther. 7:2012–2021. 2008.PubMed/NCBI View Article : Google Scholar | |
|
Huynh J, Chand A, Gough D and Ernst M: Therapeutically exploiting STAT3 activity in cancer-using tissue repair as a road map. Nat Rev Cancer. 19:82–96. 2019.PubMed/NCBI View Article : Google Scholar | |
|
Hu X, li J, Fu M, Zhao X and Wang W: The JAK/STAT signaling pathway: From bench to clinic. Signal Transduct Target Ther. 6(402)2021.PubMed/NCBI View Article : Google Scholar | |
|
Seif F, Khoshmirsafa M, Aazami H, Mohsenzadegan M, Sedighi G and Bahar M: The role of JAK-STAT signaling pathway and its regulators in the fate of T helper cells. Cell Commun Signal. 15(23)2017.PubMed/NCBI View Article : Google Scholar | |
|
Cardoso AA, Jiang Y, Luo M, Reed AM, Shahda S, He Y, Maitra A, Kelley MR and Fishel ML: APE1/Ref-1 regulates STAT3 transcriptional activity and APE1/Ref-1-STAT3 dual-targeting effectively inhibits pancreatic cancer cell survival. PLoS One. 7(e47462)2012.PubMed/NCBI View Article : Google Scholar | |
|
Fishel ML, Xia H, McGeown J, McIlwain DW, Elbanna M, Craft AA, Kaimakliotis HZ, Sandusky GE, Zhang C, Pili R, et al: Antitumor activity and mechanistic characterization of APE1/Ref-1 inhibitors in bladder cancer. Mol Cancer Ther. 18:1947–1960. 2019.PubMed/NCBI View Article : Google Scholar | |
|
Pawlus MR, Wang L and Hu CJ: STAT3 and HIF1α cooperatively activate HIF1 target genes in MDA-MB-231 and RCC4 cells. Oncogene. 33:1670–1679. 2014.PubMed/NCBI View Article : Google Scholar | |
|
Dinarello A, Betto RM, Diamante L, Tesoriere A, Ghirardo R, Cioccarelli C, Meneghetti G, Peron M, Laquatra C, Tiso N, et al: STAT3 and HIF1α cooperatively mediate the transcriptional and physiological responses to hypoxia. Cell Death Discov. 9(226)2023.PubMed/NCBI View Article : Google Scholar | |
|
Rad E, Dodd K, Thomas L, Upadhyaya M and Tee A: STAT3 and HIF1α signaling drives oncogenic cellular phenotypes in malignant peripheral nerve sheath tumors. Mol Cancer Res. 13:1149–1160. 2015.PubMed/NCBI View Article : Google Scholar | |
|
Bhakat KK, Mantha AK and Mitra S: Transcriptional regulatory functions of mammalian AP-endonuclease (APE1/Ref-1), an essential multifunctional protein. Antioxid Redox Signal. 11:621–638. 2009.PubMed/NCBI View Article : Google Scholar | |
|
Wu HH, Cheng YW, Chang JT, Wu TC, Liu WS, Chen CY and Lee H: Subcellular localization of apurinic endonuclease 1 promotes lung tumor aggressiveness via NF-kappaB activation. Oncogene. 29:4330–4340. 2010.PubMed/NCBI View Article : Google Scholar | |
|
Huang TT, Wuerzberger-Davis SM, Wu ZH and Miyamoto S: Sequential modification of NEMO/IKKgamma by SUMO-1 and ubiquitin mediates NF-kappaB activation by genotoxic stress. Cell. 115:565–576. 2003.PubMed/NCBI View Article : Google Scholar | |
|
Xia L, Tan S, Zhou Y, Lin J, Wang H, Oyang L, Tian Y, Liu L, Su M, Wang H, et al: Role of the NFκB-signaling pathway in cancer. Onco Targets Ther. 11:2063–2073. 2018.PubMed/NCBI View Article : Google Scholar | |
|
Siqueira PB, de Sousa Rodrigues MM, de Amorim ÍSS, da Silva TG, da Silva Oliveira M, Rodrigues JA, de Souza da Fonseca A and Mencalha AL: The APE1/REF-1 and the hallmarks of cancer. Mol Biol Rep. 51(47)2024.PubMed/NCBI View Article : Google Scholar | |
|
Shin JH, Choi S, Lee YR, Park MS, Na YG, Irani K, Lee SD, Park JB, Kim JM, Lim JS and Jeon BH: APE1/Ref-1 as a serological biomarker for the detection of bladder cancer. Cancer Res Treat. 47:823–833. 2015.PubMed/NCBI View Article : Google Scholar | |
|
Luo M and Kelley MR: Inhibition of the human apurinic/apyrimidinic endonuclease (APE1) repair activity and sensitization of breast cancer cells to DNA alkylating agents with lucanthone. Anticancer Res. 24:2127–2134. 2004.PubMed/NCBI | |
|
Long K, Gu L, Li L, Zhang Z, Li E, Zhang Y, He L, Pan F, Guo Z and Hu Z: Small-molecule inhibition of APE1 induces apoptosis, pyroptosis, and necroptosis in non-small cell lung cancer. Cell Death Dis. 12(503)2021.PubMed/NCBI View Article : Google Scholar | |
|
Fishel ML, He Y, Reed AM, Chin-Sinex H, Hutchins GD, Mendonca MS and Kelley MR: Knockdown of the DNA repair and redox signaling protein Ape1/Ref-1 blocks ovarian cancer cell and tumor growth. DNA Repair (Amst). 7:177–186. 2008.PubMed/NCBI View Article : Google Scholar | |
|
Deng X, Zhen P, Niu X, Dai Y, Wang Y and Zhou M: APE1 promotes proliferation and migration of cutaneous squamous cell carcinoma. J Dermatol Sci. 100:67–74. 2020.PubMed/NCBI View Article : Google Scholar | |
|
Yang Z, Yang S, Misner BJ, Liu-Smith F and Meyskens FL: The role of APE/Ref-1 signaling pathway in hepatocellular carcinoma progression. Int J Oncol. 45:1820–1828. 2014.PubMed/NCBI View Article : Google Scholar | |
|
Singh AK, Kumar R and Pandey AK: Hepatocellular carcinoma: Causes, mechanism of progression and biomarkers. Curr Chem Genom Transl Med. 12:9–26. 2018.PubMed/NCBI View Article : Google Scholar | |
|
Tell G, Quadrifoglio F, Tiribelli C and Kelley MR: The many functions of APE1/Ref-1: Not only a DNA repair enzyme. Antioxid Redox Signal. 11:601–620. 2009.PubMed/NCBI View Article : Google Scholar | |
|
Sheng Q, Zhang Y, Wang R, Zhang J, Chen B, Wang J, Zhang W and Xin X: Prognostic significance of APE1 cytoplasmic localization in human epithelial ovarian cancer. Med Oncol. 29:1265–1271. 2012.PubMed/NCBI View Article : Google Scholar | |
|
Bazzani V, Barchiesi A, Radecka D, Pravisani R, Guadagno A, Di Loreto C, Baccarani U and Vascotto C: Mitochondrial apurinic/apyrimidinic endonuclease 1 enhances mtDNA repair contributing to cell proliferation and mitochondrial integrity in early stages of hepatocellular carcinoma. BMC Cancer. 20(969)2020.PubMed/NCBI View Article : Google Scholar | |
|
Wu HH, Chu YC, Wang L, Tsai LH, Lee MC, Chen CY, Shieh SH, Cheng YW and Lee H: Cytoplasmic Ape1 Expression Elevated by p53 aberration may predict survival and relapse in resected non-small cell lung cancer. Ann Surg Oncol. 20 (Suppl 3):S336–S347. 2013.PubMed/NCBI View Article : Google Scholar | |
|
Abbotts R and Madhusudan S: Human AP endonuclease 1 (APE1): From mechanistic insights to druggable target in cancer. Cancer Treat Rev. 36:425–435. 2010.PubMed/NCBI View Article : Google Scholar | |
|
Malfatti MC, Bellina A, Antoniali G and Tell G: Revisiting two decades of research focused on targeting APE1 for cancer therapy: The pros and cons. Cells. 12(1895)2023.PubMed/NCBI View Article : Google Scholar | |
|
Kumar S, Zhao J, Talluri S, Buon L, Mu S, Potluri LB, Liao C, Shi J, Chakraborty C, Gonzalez GB, et al: Elevated APE1 dysregulates homologous recombination and cell cycle driving genomic evolution, tumorigenesis, and chemoresistance in esophageal adenocarcinoma. Gastroenterology. 165:357–373. 2023.PubMed/NCBI View Article : Google Scholar | |
|
Wang D, Xiang DB, Yang XQ, Chen LS, Li MX, Zhong ZY and Zhang YS: APE1 overexpression is associated with cisplatin resistance in non-small cell lung cancer and targeted inhibition of APE1 enhances the activity of cisplatin in A549 cells. Lung Cancer. 66:298–304. 2009.PubMed/NCBI View Article : Google Scholar | |
|
Franchi LP, de Freitas Lima JEB, Piva HL and Tedesco AC: The redox function of apurinic/apyrimidinic endonuclease 1 as key modulator in photodynamic therapy. J Photochem Photobiol B. 211(111992)2020.PubMed/NCBI View Article : Google Scholar | |
|
Zhou J, Wei Z, Yang C, Jia D, Pan B, Zeng Y, Sun D and Yu Y: APE1 promotes radiation resistance against radiation-induced pyroptosis by inhibiting the STING pathway in lung adenocarcinoma. Transl Oncol. 36(101749)2023.PubMed/NCBI View Article : Google Scholar | |
|
Li Y, Zhao X, Xiao H, Yang B, Liu J, Rao W, Dai X, Li M, Dai N, Yang Y and Wang D: APE1 may influence CD4+ naïve T cells on recurrence free survival in early stage NSCLC. BMC Cancer. 21(233)2021.PubMed/NCBI View Article : Google Scholar | |
|
Woo J, Park H, Sung SH, Moon BI, Suh H and Lim W: Prognostic Value of Human Apurinic/Apyrimidinic Endonuclease 1 (APE1) Expression in Breast Cancer. PLoS One. 9(e99528)2014.PubMed/NCBI View Article : Google Scholar | |
|
Lee SG, Lee DG, Joo YH and Chung N: Synergistic inhibitory effects of the oxyresveratrol and dacarbazine combination against melanoma cells. Oncol Lett. 22(667)2021.PubMed/NCBI View Article : Google Scholar | |
|
Gómez-Zorita S, González-Arceo M, Fernández-Quintela A, Eseberri I, Trepiana J and Portillo MP: Scientific evidence supporting the beneficial effects of isoflavones on human health. Nutrients. 12(3853)2020.PubMed/NCBI View Article : Google Scholar | |
|
Sui J, Li M, Qian C, Wang S, Cheng Y, Chen BP and Wang D: Functional analysis of tanshinone IIA that blocks the redox function of human apurinic/apyrimidinic endonuclease 1/redox factor-1. Drug Des Devel Ther. 8:2147–2160. 2014.PubMed/NCBI View Article : Google Scholar | |
|
Cesaratto L, Codarin E, Vascotto C, Leonardi A, Kelley MR, Tiribelli C and Tell G: Specific inhibition of the redox activity of ape1/ref-1 by e3330 blocks tnf-α-induced activation of IL-8 production in liver cancer cell lines. PLoS One. 8(e70909)2013.PubMed/NCBI View Article : Google Scholar | |
|
Kang S, Wang Z, Li B, Gao X, He W, Cao S, Cai Y and Chen H: Anti-tumor effects of resveratrol on malignant melanoma is associated with promoter demethylation of RUNX3 gene. Pharmazie. 74:163–167. 2019.PubMed/NCBI View Article : Google Scholar | |
|
Laev SS, Salakhutdinov NF and Lavrik OI: Inhibitors of nuclease and redox activity of apurinic/apyrimidinic endonuclease 1/redox effector factor 1 (APE1/Ref-1). Bioorg Med Chem. 25:2531–2544. 2017.PubMed/NCBI View Article : Google Scholar | |
|
Kim IS: Current perspectives on the beneficial effects of soybean isoflavones and their metabolites for humans. Antioxidants (Basel). 10(1064)2021.PubMed/NCBI View Article : Google Scholar | |
|
Hillman GG: Soy isoflavones protect normal tissues while enhancing radiation responses. Semin Radiat Oncol. 29:62–71. 2019.PubMed/NCBI View Article : Google Scholar | |
|
Singh-Gupta V, Joiner MC, Runyan L, Yunker CK, Sarkar FH, Miller S, Gadgeel SM, Konski AA and Hillman GG: Soy isoflavones augment radiation effect by inhibiting APE1/Ref-1 DNA repair activity in non-small cell lung cancer. J Thorac Oncol. 6:688–698. 2011.PubMed/NCBI View Article : Google Scholar | |
|
Su D, Delaplane S, Luo M, Rempel DL, Vu B, Kelley MR, Gross ML and Georgiadis MM: Interactions of apurinic/apyrimidinic endonuclease with a redox inhibitor: Evidence for an alternate conformation of the enzyme. Biochemistry. 50:82–92. 2011.PubMed/NCBI View Article : Google Scholar | |
|
Luo M, Delaplane S, Jiang A, Reed A, He Y, Fishel M, Nyland RL II, Borch RF, Qiao X, Georgiadis MM and Kelley MR: Role of the multifunctional DNA repair and redox signaling protein Ape1/Ref-1 in cancer and endothelial cells: Small-molecule inhibition of the redox function of Ape1. Antioxid Redox Signal. 10:1853–1867. 2008.PubMed/NCBI View Article : Google Scholar | |
|
Zou GM, Karikari C, Kabe Y, Handa H, Anders RA and Maitra A: The Ape-1/Ref-1 redox antagonist E3330 inhibits the growth of tumor endothelium and endothelial progenitor cells: Therapeutic implications in tumor angiogenesis. J Cell Physiol. 219:209–218. 2009.PubMed/NCBI View Article : Google Scholar | |
|
Sengupta S, Mantha AK, Mitra S and Bhakat KK: Human AP endonuclease (APE1/Ref-1) and its acetylation regulate YB-1-p300 recruitment and RNA polymerase II loading in the drug-induced activation of multidrug resistance gene MDR1. Oncogene. 30:482–493. 2011.PubMed/NCBI View Article : Google Scholar | |
|
Du Y, Zhou Y, Yan X, Pan F, He L, Guo Z and Hu Z: APE1 inhibition enhances ferroptotic cell death and contributes to hepatocellular carcinoma therapy. Cell Death Differ. 31:431–446. 2024.PubMed/NCBI View Article : Google Scholar | |
|
Sadek K, Abouzed T, Nasr S and Shoukry M: Licochalcone B ameliorates liver cancer via targeting of apoptotic genes, DNA repair systems, and cell cycle control. Iran J Pharm Res. 19:372–386. 2020.PubMed/NCBI View Article : Google Scholar | |
|
Sadek K, Abouzeid T, Nasr S and Shukry M: Role and potential targeting of hepatic apurinic/apyrimidinic endonuclease-1 and cyclin-dependent kinase-4 in hepatocellular carcinoma. Can J Physiol Pharmacol. 96(X)2018.PubMed/NCBI View Article : Google Scholar |
