[논문]Synergistic Induction of Apoptosis by the Combination of an Axl Inhibitor and Auranofin in Human Breast Cancer Cells

Ryu, Yeon-Sang; Shin, Sangyun; An, Hong-Gyu; Kwon, Tae-Uk; Baek, Hyoung-Seok; Kwon, Yeo-Jung; Chun, Young-Jin

doi:10.4062/biomolther.2020.051

Synergistic Induction of Apoptosis by the Combination of an Axl Inhibitor and Auranofin in Human Breast Cancer Cells 원문보기

Biomolecules & therapeutics, v.28 no.5, 2020년, pp.473 - 481

Ryu, Yeon-Sang (Center for Metareceptome Research, College of Pharmacy, Chung-Ang University) , Shin, Sangyun (Center for Metareceptome Research, College of Pharmacy, Chung-Ang University) , An, Hong-Gyu (Center for Metareceptome Research, College of Pharmacy, Chung-Ang University) , Kwon, Tae-Uk (Center for Metareceptome Research, College of Pharmacy, Chung-Ang University) , Baek, Hyoung-Seok (Center for Metareceptome Research, College of Pharmacy, Chung-Ang University) , Kwon, Yeo-Jung (Center for Metareceptome Research, College of Pharmacy, Chung-Ang University) , Chun, Young-Jin (Center for Metareceptome Research, College of Pharmacy, Chung-Ang University)

Abstract ▼ AI-Helper

Axl receptor tyrosine kinase has been implicated in cancer progression, invasion, and metastasis in various cancer types. Axl overexpression has been observed in many cancers, and selective inhibitors of Axl, including R428, may be promising therapeutic agents for several human cancers, such as breast, lung, and pancreatic cancers. Here, we examined the cell growth inhibition mediated by R428 and auranofin individually as well as in combination in the human breast cancer cell lines MCF-7 and MDA-MB-231 to identify new advanced combination treatments for human breast cancer. Our data showed that combination therapy with R428 and auranofin markedly inhibited cancer cell proliferation. Isobologram analyses of these cells indicated a clear synergism between R428 and auranofin with a combination index value of 0.73. The combination treatment promoted apoptosis as indicated by caspase 3 activation and poly (ADP-ribose) polymerase cleavage. Cancer cell migration was also significantly inhibited by this combination treatment. Moreover, we found that combination therapy significantly increased the expression level of Bax, a mitochondrial proapoptotic factor, but decreased that of the X-linked inhibitor of apoptosis protein. Furthermore, the suppression of cell viability and induction of Bax expression by the combination treatment were recovered by treatment with N-acetylcysteine. In conclusion, our data demonstrated that combined treatment with R428 and auranofin synergistically induced apoptosis in human breast cancer cells and may thus serve as a novel and valuable approach for cancer therapy.

주제어

참고문헌 (40)

Bayat Mokhtari R. Homayouni T. S. Baluch N. Morgatskaya E. Kumar S. Das B. Yeger H. 2017 Combination therapy in combating cancer Oncotarget 8 38022 38043 10.18632/oncotarget.16723 28410237

상세보기
Cazanave S. C. Wang X. Zhou H. Rahmani M. Grant S. Durrant D. E. Klaassen C. D. Yamamoto M. Sanyal A. J. 2014 Degradation of Keap1 activates BH3-only proteins Bim and PUMA during hepatocyte lipoapoptosis Cell Death Differ. 21 1303 1312 10.1038/cdd.2014.49 24769730

상세보기
Chu C. Gao X. Li X. Zhang X. Ma R. Jia Y. Li D. Wang D. Xu F. 2020 Involvement of estrogen receptor-α in the activation of Nrf2-antioxidative signaling pathways by silibinin in pancreatic β-cells Biomol. Ther. (Seoul) 28 163 171 10.4062/biomolther.2019.071 31649209

원문보기 상세보기
Cuadrado A. Manda G. Hassan A. Alcaraz M. J. Barbas C. Daiber A. Ghezzi P. Leon R. Lopez M. G. Oliva B. Pajares M. Rojo A. I. Robledinos-Anton N. Valverde A. M. Guney E. Schmidt H. 2018 Transcription factor NRF2 as a therapeutic target for chronic diseases: a systems medicine approach Pharmacol. Rev. 70 348 383 10.1124/pr.117.014753 29507103

상세보기
Cuadrado A. Martin-Moldes Z. Ye J. Lastres-Becker I. 2014 Transcription factors NRF2 and NF-κB are coordinated effectors of the Rho family, GTP-binding protein RAC1 during inflammation J. Biol. Chem. 289 15244 15258 10.1074/jbc.M113.540633 24759106

상세보기
Faix J. Weber I. 2013 A dual role model for active Rac1 in cell migration Small GTPases 4 110 115 10.4161/sgtp.23476 23503127

상세보기
Fiskus W. Saba N. Shen M. Ghias M. Liu J. Gupta S. D. Chauhan L. Rao R. Gunewardena S. Schorno K. Austin C. P. Maddocks K. Byrd J. Melnick A. Huang P. Wiestner A. Bhalla K. N. 2014 Auranofin induces lethal oxidative and endoplasmic reticulum stress and exerts potent preclinical activity against chronic lymphocytic leukemia Cancer Res. 74 2520 2532 10.1158/0008-5472.CAN-13-2033 24599128

상세보기
Gay C. M. Balaji K. Byers L. A. 2017 Giving AXL the axe: targeting AXL in human malignancy Br. J. Cancer 116 415 423 10.1038/bjc.2016.428 28072762

상세보기
Gelmon K. Dent R. Mackey J. R. Laing K. McLeod D. Verma S. 2012 Targeting triple-negative breast cancer: optimising therapeutic outcomes Ann. Oncol. 23 2223 2234 10.1093/annonc/mds067 22517820

상세보기
Goyette M. A. Duhamel S. Aubert L. Pelletier A. Savage P. Thibault M. P. Johnson R. M. Carmeliet P. Basik M. Gaboury L. Muller W. J. Park M. Roux P. P. Gratton J. P. Cote J. F. 2018 The receptor tyrosine kinase Axl is required at multiple steps of the metastatic cascade during HER2-positive breast cancer progression Cell Rep. 23 1476 1490 10.1016/j.celrep.2018.04.019 29719259

상세보기
Holland S. J. Pan A. Franci C. Hu Y. Chang B. Li W. Duan M. Torneros A. Yu J. Heckrodt T. J. Zhang J. Ding P. Apatira A. Chua J. Brandt R. Pine P. Goff D. Singh R. Payan D. G. Hitoshi Y. 2010 R428, a selective small molecule inhibitor of Axl kinase, blocks tumor spread and prolongs survival in models of metastatic breast cancer Cancer Res. 70 1544 1554 10.1158/0008-5472.CAN-09-2997 20145120

상세보기
Jin S. Ye K. 2013 Targeted drug delivery for breast cancer treatment Recent Pat. Anticancer Drug Discov. 8 143 153 10.2174/1574892811308020003 23394116
Jung J. 2019 Role of G protein-coupled estrogen receptor in cancer progression Toxicol. Res. 35 209 214 10.5487/TR.2019.35.3.209 31341549

원문보기 상세보기
Kapur A. Beres T. Rathi K. Nayak A. P. Czarnecki A. Felder M. Gillette A. Ericksen S. S. Sampene E. Skala M. C. Barroilhet L. Patankar M. S. 2018 Oxidative stress via inhibition of the mitochondrial electron transport and Nrf-2-mediated anti-oxidative response regulate the cytotoxic activity of plumbagin Sci. Rep. 8 1073 10.1038/s41598-018-19261-w 29348410

상세보기
Katoh H. Hiramoto K. Negishi M. 2006 Activation of Rac1 by RhoG regulates cell migration J. Cell Sci. 119 56 65 10.1242/jcs.02720 16339170

상세보기
Katz H. Alsharedi M. 2017 Immunotherapy in triple-negative breast cancer Med. Oncol. 35 13 10.1007/s12032-017-1071-6 29255938

상세보기
Koorstra J. B. Karikari C. A. Feldmann G. Bisht S. Rojas P. L. Offerhaus G. J. Alvarez H. Maitra A. 2009 The Axl receptor tyrosine kinase confers an adverse prognostic influence in pancreatic cancer and represents a new therapeutic target Cancer Biol. Ther. 8 618 626 10.4161/cbt.8.7.7923 19252414

상세보기
Leconet W. Chentouf M. du Manoir S. Chevalier C. Sirvent A. Ait-Arsa I. Busson M. Jarlier M. Radosevic-Robin N. Theillet C. Chalbos D. Pasquet J. M. Pelegrin A. Larbouret C. Robert B. 2017 Therapeutic activity of anti-Axl antibody against triple-negative breast cancer patient-derived xenografts and metastasis Clin. Cancer Res. 23 2806 2816 10.1158/1078-0432.CCR-16-1316 27923843

상세보기
Lee J. E. Kwon Y. J. Baek H. S. Ye D. J. Cho E. Choi H. K. Oh K. S. Chun Y. J. 2017 Synergistic induction of apoptosis by combination treatment with mesupron and auranofin in human breast cancer cells Arch. Pharm. Res. 40 746 759 10.1007/s12272-017-0923-0 28560500

상세보기
Lee W. P. Wen Y. Varnum B. Hung M. C. 2002 Akt is required for Axl-Gas6 signaling to protect cells from E1A-mediated apoptosis Oncogene 21 329 336 10.1038/sj.onc.1205066 11821945

상세보기
Lu K. Alcivar A. L. Ma J. Foo T. K. Zywea S. Mahdi A. Huo Y. Kensler T. W. Gatza M. L. Xia B. 2017 NRF2 induction supporting breast cancer cell survival is enabled by oxidative stress-induced DPP3-Keap1 interaction Cancer Res. 77 2881 2892 10.1158/0008-5472.CAN-16-2204 28416489

상세보기
Maes M. E. Schlamp C. L. Nickells R. W. 2017 Live-cell imaging to measure Bax recruitment kinetics to mitochondria during apoptosis PLoS ONE 12 e0184434 10.1371/journal.pone.0184434 28880942

상세보기
Miller M. A. Oudin M. J. Sullivan R. J. Wang S. J. Meyer A. S. Im H. Frederick D. T. Tadros J. Griffith L. G. Lee H. Weissleder R. Flaherty K. T. Gertler F. B. Lauffenburger D. A. 2016 Reduced proteolytic shedding of receptor tyrosine kinases is a post-translational mechanism of kinase inhibitor resistance Cancer Discov. 6 382 399 10.1158/2159-8290.CD-15-0933 26984351

상세보기
Mine N. Yamamoto S. Kufe D. W. Von Hoff D. D. Kawabe T. 2014 Activation of Nrf2 pathways correlates with resistance of NSCLC cell lines to CBP501 in vitro Mol. Cancer Ther. 13 2215 2225 10.1158/1535-7163.MCT-13-0808 25053821

상세보기
Nagini S. 2017 Breast cancer: current molecular therapeutic targets and new players Anticancer Agents Med. Chem. 17 152 163 10.2174/1871520616666160502122724 27137076

상세보기
Oommen D. Yiannakis D. Jha A. N. 2016 BRCA1 deficiency increases the sensitivity of ovarian cancer cells to auranofin Mutat. Res. 784 785 8 15 10.1016/j.mrfmmm.2015.11.002 26731315

상세보기
Pawlowski J. Kraft A. S. 2000 Bax-induced apoptotic cell death Proc. Natl. Acad. Sci. U.S.A. 97 529 531 10.1073/pnas.97.2.529 10639111

상세보기
Probst B. L. McCauley L. Trevino I. Wigley W. C. Ferguson D. A. 2015 Cancer cell growth is differentially affected by constitutive activation of NRF2 by Keap1 deletion and pharmacological activation of NRF2 by the synthetic triterpenoid, RTA 405 PLoS ONE 10 e0135257 10.1371/journal.pone.0135257 26301506

상세보기
Richa S. Dey P. Park C. Yang J. Son J. Y. Park J. H. Lee S. H. Ahn M. Y. Kim I. S. Moon H. R. Kim H. S. 2020 A new histone deacetylase inhibitor, MHY4381, induces apoptosis via generation of reactive oxygen species in human prostate cancer cells Biomol. Ther. (Seoul) 28 184 194 10.4062/biomolther.2019.074 31476841

원문보기 상세보기
Shamas-Din A. Kale J. Leber B. Andrews D. W. 2013 Mechanisms of action of Bcl-2 family proteins Cold Spring Harb. Perspect. Biol. 5 a008714 10.1101/cshperspect.a008714 23545417

상세보기
Shaw I. C. 1999 Gold-based therapeutic agents Chem. Rev. 99 2589 2600 10.1021/cr980431o 11749494

상세보기
Sun S. Y. 2010 N-acetylcysteine, reactive oxygen species and beyond Cancer Biol. Ther. 9 109 110 10.4161/cbt.9.2.10583 19949311

상세보기
Tallarida R. J. 2001 Drug synergism: its detection and applications J. Pharmacol. Exp. Ther. 298 865 872 11504778

상세보기
Tang B. Tang F. Wang Z. Qi G. Liang X. Li B. Yuan S. Liu J. Yu S. He S. 2016 Upregulation of Akt/NF-κB-regulated inflammation and Akt/Bad-related apoptosis signaling pathway involved in hepatic carcinoma process: suppression by carnosic acid nanoparticle Int. J. Nanomedicine 11 6401 6420 10.2147/IJN.S101285 27942213

상세보기
Varghese E. Busselberg D. 2014 Auranofin, an anti-rheumatic gold compound, modulates apoptosis by elevating the intracellular calcium concentration in MCF-7 breast cancer cells Cancers (Basal) 6 2243 2258 10.3390/cancers6042243 25383481

상세보기
Vidula N. Bardia A. 2017 Targeted therapy for metastatic triple negative breast cancer: the next frontier in precision oncology Oncotarget 8 106167 106168 10.18632/oncotarget.22580 29290935

상세보기
Wang C. Jin H. Wang N. Fan S. Wang Y. Zhang Y. Wei L. Tao X. Gu D. Zhao F. Fang J. Yao M. Qin W. 2016 Gas6/Axl axis contributes to chemoresistance and metastasis in breast cancer through kat/GSK-3β/β-catenin signaling Theranostics 6 1205 1219 10.7150/thno.15083 27279912

상세보기
Yao H. He G. Yan S. Chen C. Song L. Rosol T. J. Deng X. 2017 Triple-negative breast cancer: is there a treatment on the horizon Oncotarget 8 1913 1924 10.18632/oncotarget.12284 27765921

상세보기
Zhang P. Singh A. Yegnasubramanian S. Esopi D. Kombairaju P. Bodas M. Wu H. Bova S. G. Biswal S. 2010 Loss of Kelch-like ECH-associated protein 1 function in prostate cancer cells causes chemoresistance and radioresistance and promotes tumor growth Mol. Cancer Ther. 9 336 346 10.1158/1535-7163.MCT-09-0589 20124447

상세보기
Zhang Y. X. Knyazev P. G. Cheburkin Y. V. Sharma K. Knyazev Y. P. Orfi L. Szabadkai I. Daub H. Keri G. Ullrich A. 2008 Axl is a potential target for therapeutic intervention in breast cancer progression Cancer Res. 68 1905 1915 10.1158/0008-5472.CAN-07-2661 18339872

상세보기

LOADING...

표제어: PCR

동의어: Packet Collision Rate

용어 설명 출처 목록 (6)

용어 설명: PCR은 세균 특이성이 있는 primer를 이용하여 적은 수의 세균이 있을지라도 쉽게 검출할 수 있는 유용한 방법이며, 이를 이용하여 구강 내 치면세균막이나 타액에서 직접 세균을 검출할 수 있게 되었다[8].

내보내기 구분	파일저장 인쇄 메일전송
구성항목	기본정보 상세정보 관리번호, 논문명, 저널/프로시딩명, 저자 , 발행년, 권, 호, 시작페이지, 끝페이지, 발행기관 관리번호, 논문명, 대등논문명, 저자 , 저널/프로시딩명, 발행기관, 발행년, 발행언어, 권, 호, 시작페이지, 끝페이지, ISBN, ISSN, 주제분야, 키워드, 초록(한글), 초록(영문), 저자(소속기관)
저장형식	Text(ASCII format) Excel format RefWorks Direct Export RIS format (for Reference Manager, ProCite, EndNote), Scholar's Aids, Mendeley
메일정보	받는사람 (필수) @ 보내는사람 (선택) @ 제목 내용 KISTI 검색결과 이메일 서비스
안내	총 건의 자료가 검색되었습니다. 다운받으실 자료의 인덱스를 입력하세요. (1-10,000) 검색결과의 순서대로 최대 10,000건 까지 다운로드가 가능합니다. 데이타가 많을 경우 속도가 느려질 수 있습니다.(최대 2~3분 소요) 다운로드 파일은 UTF-8 형태로 저장됩니다. 파일의 내용이 제대로 보이지 않을실 때는 웹브라우저 상단의 보기 -> 인코딩 -> 자동선택 여부를 확인하십시오. ~ Text(ASCII format) Excel format

연합인증

Synergistic Induction of Apoptosis by the Combination of an Axl Inhibitor and Auranofin in Human Breast Cancer Cells 원문보기

Abstract ▼ AI-Helper

주제어

참고문헌 (40)

이 논문을 인용한 문헌

연구과제 타임라인

관련 콘텐츠

원문 보기

원문 URL 링크

오픈액세스(OA) 유형

이 논문과 함께 이용한 콘텐츠

AI-Helper ※ AI-Helper는 오픈소스 모델을 사용합니다.

선택된 텍스트

연합인증

Synergistic Induction of Apoptosis by the Combination of an Axl Inhibitor and Auranofin in Human Breast Cancer Cells 원문보기

Abstract ▼ AI-Helper

주제어

참고문헌 (40)

이 논문을 인용한 문헌

연구과제 타임라인

전체(0) 논문(0) 특허(0) 보고서(0)

전체(0) 논문(0) 특허(0) 보고서(0)

관련 콘텐츠

원문 보기

원문 URL 링크

오픈액세스(OA) 유형

이 논문과 함께 이용한 콘텐츠

AI-Helper ※ AI-Helper는 오픈소스 모델을 사용합니다.

선택된 텍스트