Top

Cancer Chemotherapy and Pharmacology

Published in:

01-03-2017 | Original Article

Curcumin suppresses cisplatin resistance development partly via modulating extracellular vesicle-mediated transfer of MEG3 and miR-214 in ovarian cancer

Authors: Jing Zhang, Jinyu Liu, Xinyan Xu, Li Li

Published in: Cancer Chemotherapy and Pharmacology | Issue 3/2017

Abstract

Purpose

To investigate how curcumin alters the extracellular vesicles’ (EVs) capability to ship drug resistance in ovarian cancer.

Methods

The EVs from cisplatin-resistant A2780cp cells with curcumin treatment (EVs-CU) or without curcumin treatment (EVs-N) were collected for lncRNA profiling. Curcumin’s effect on MEG3 promoter methylation and MEG3 expression were studied by MSP and qRT-PCR, respectively. The regulative effect of MEG3 on miR-214 expression and the functional role of EVs mediated transfer of miR-214 in cisplatin resistance were further investigated.

Results

Curcumin weakened the EVs-N’s capability to induce drug resistance and induced significant changes of lncRNAs in the EVs. MEG3 is one of the most upregulated lncRNAs. Curcumin led to demethylation in the promoter region of MEG3 and 5-AZA-dC treatment restored MEG3 expression in a dose dependent manner. There were at least two binding sites between MEG3 and miR-214. MEG3 restoration by curcumin significantly reduced miR-214 in cells and in EVs. Functionally, miR-214 inhibition weakened the EVs-N’s capability to enhance chemoresistance, while miR-214 overexpression increased the capability of EVs-CU in inducing chemoresistance.

Conclusion

Curcumin can restore MEG3 levels via demethylation. MEG3 upregulation can decrease EVs mediated transfer of miR-214 in ovarian cancer cells, thereby reducing drug resistance.

Siegel R, Ma J, Zou Z, Jemal A (2014) Cancer statistics, 2014. CA Cancer J Clin 64(1):9–29. doi:10.3322/caac.21208 CrossRefPubMed

Suh DH, Kim JW, Kim K, Kang SB (2010) Major clinical research advances in gynecologic cancer in 2010. J Gynecol Oncol 21(4):209–218. doi:10.3802/jgo.2010.21.4.209 CrossRefPubMedPubMedCentral

Marchini S, Fruscio R, Clivio L, Beltrame L, Porcu L, Fuso Nerini I, Cavalieri D, Chiorino G, Cattoretti G, Mangioni C, Milani R, Torri V, Romualdi C, Zambelli A, Romano M, Signorelli M, di Giandomenico S, D’Incalci M (2013) Resistance to platinum-based chemotherapy is associated with epithelial to mesenchymal transition in epithelial ovarian cancer. Eur J Cancer 49(2):520–530. doi:10.1016/j.ejca.2012.06.026 CrossRefPubMed

da Silveira JC, Veeramachaneni DN, Winger QA, Carnevale EM, Bouma GJ (2012) Cell-secreted vesicles in equine ovarian follicular fluid contain miRNAs and proteins: a possible new form of cell communication within the ovarian follicle. Biol Reprod 86(3):71. doi:10.1095/biolreprod.111.093252 CrossRefPubMed

Takahashi K, Yan IK, Kogure T, Haga H, Patel T (2014) Extracellular vesicle-mediated transfer of long non-coding RNA ROR modulates chemosensitivity in human hepatocellular cancer. FEBS Open Biol 4:458–467. doi:10.1016/j.fob.2014.04.007 CrossRef

Nawaz M, Fatima F, Nazarenko I, Ekstrom K, Murtaza I, Anees M, Sultan A, Neder L, Camussi G, Valadi H, Squire JA, Kislinger T (2016) Extracellular vesicles in ovarian cancer: applications to tumor biology, immunotherapy and biomarker discovery. Expert Rev Proteom 13(4):395–409. doi:10.1586/14789450.2016.1165613 CrossRef

Au Yeung CL, Co NN, Tsuruga T, Yeung TL, Kwan SY, Leung CS, Li Y, Lu ES, Kwan K, Wong KK, Schmandt R, Lu KH, Mok SC (2016) Exosomal transfer of stroma-derived miR21 confers paclitaxel resistance in ovarian cancer cells through targeting APAF1. Nat Commun 7:11150. doi:10.1038/ncomms11150 CrossRefPubMedPubMedCentral

Terlikowska KM, Witkowska AM, Zujko ME, Dobrzycka B, Terlikowski SJ (2014) Potential application of curcumin and its analogues in the treatment strategy of patients with primary epithelial ovarian cancer. Int J Mol Sci 15(12):21703–21722. doi:10.3390/ijms151221703 CrossRefPubMedPubMedCentral

Taverna S, Giallombardo M, Pucci M, Flugy A, Manno M, Raccosta S, Rolfo C, De Leo G, Alessandro R (2015) Curcumin inhibits in vitro and in vivo chronic myelogenous leukemia cells growth: a possible role for exosomal disposal of miR-21. Oncotarget 6(26):21918–21933. doi:10.18632/oncotarget.4204 CrossRefPubMedPubMedCentral

10.

Abouzeid AH, Patel NR, Torchilin VP (2014) Polyethylene glycol-phosphatidylethanolamine (PEG-PE)/vitamin E micelles for co-delivery of paclitaxel and curcumin to overcome multi-drug resistance in ovarian cancer. Int J Pharm 464(1–2):178–184. doi:10.1016/j.ijpharm.2014.01.009 CrossRefPubMedPubMedCentral

11.

Kogure T, Patel T (2013) Isolation of extracellular nanovesicle microRNA from liver cancer cells in culture. Methods Mol Biol 1024:11–18. doi:10.1007/978-1-62703-453-1_2 CrossRefPubMed

12.

Takahashi K, Yan IK, Wood J, Haga H, Patel T (2014) Involvement of extracellular vesicle long noncoding RNA (linc-VLDLR) in tumor cell responses to chemotherapy. Mol Cancer Res 12(10):1377–1387. doi:10.1158/1541-7786.MCR-13-0636 CrossRefPubMedPubMedCentral

13.

Sheng X, Li J, Yang L, Chen Z, Zhao Q, Tan L, Zhou Y, Li J (2014) Promoter hypermethylation influences the suppressive role of maternally expressed 3, a long non-coding RNA, in the development of epithelial ovarian cancer. Oncol Rep 32(1):277–285. doi:10.3892/or.2014.3208 PubMed

14.

Yang H, Kong W, He L, Zhao JJ, O’Donnell JD, Wang J, Wenham RM, Coppola D, Kruk PA, Nicosia SV, Cheng JQ (2008) MicroRNA expression profiling in human ovarian cancer: miR-214 induces cell survival and cisplatin resistance by targeting PTEN. Cancer Res 68(2):425–433. doi:10.1158/0008-5472.CAN-07-2488 CrossRefPubMed

15.

Xu CX, Xu M, Tan L, Yang H, Permuth-Wey J, Kruk PA, Wenham RM, Nicosia SV, Lancaster JM, Sellers TA, Cheng JQ (2012) MicroRNA miR-214 regulates ovarian cancer cell stemness by targeting p53/Nanog. J Biol Chem 287(42):34970–34978. doi:10.1074/jbc.M112.374611 CrossRefPubMedPubMedCentral

16.

Safaei R, Larson BJ, Cheng TC, Gibson MA, Otani S, Naerdemann W, Howell SB (2005) Abnormal lysosomal trafficking and enhanced exosomal export of cisplatin in drug-resistant human ovarian carcinoma cells. Mol Cancer Ther 4(10):1595–1604. doi:10.1158/1535-7163.MCT-05-0102 CrossRefPubMed

17.

Pink RC, Samuel P, Massa D, Caley DP, Brooks SA, Carter DR (2015) The passenger strand, miR-21-3p, plays a role in mediating cisplatin resistance in ovarian cancer cells. Gynecol Oncol 137(1):143–151. doi:10.1016/j.ygyno.2014.12.042 CrossRefPubMed

18.

Weiner-Gorzel K, Dempsey E, Milewska M, McGoldrick A, Toh V, Walsh A, Lindsay S, Gubbins L, Cannon A, Sharpe D, O’Sullivan J, Murphy M, Madden SF, Kell M, McCann A, Furlong F (2015) Overexpression of the microRNA miR-433 promotes resistance to paclitaxel through the induction of cellular senescence in ovarian cancer cells. Cancer Med 4(5):745–758. doi:10.1002/cam4.409 CrossRefPubMedPubMedCentral

19.

Zhang FF, Zhu YF, Zhao QN, Yang DT, Dong YP, Jiang L, Xing WX, Li XY, Xing H, Shi M, Chen Y, Bruce IC, Jin J, Ma X (2014) Microvesicles mediate transfer of P-glycoprotein to paclitaxel-sensitive A2780 human ovarian cancer cells, conferring paclitaxel-resistance. Eur J Pharmacol 738:83–90. doi:10.1016/j.ejphar.2014.05.026 CrossRefPubMed

20.

Zhang J, Yao T, Wang Y, Yu J, Liu Y, Lin Z (2016) Long noncoding RNA MEG3 is downregulated in cervical cancer and affects cell proliferation and apoptosis by regulating miR-21. Cancer Biol Ther 17 (1):104–113. doi:10.1080/15384047.2015.1108496 CrossRefPubMed

21.

Liu LX, Deng W, Zhou XT, Chen RP, Xiang MQ, Guo YT, Pu ZJ, Li R, Wang GF, Wu LF (2016) The mechanism of adenosine-mediated activation of lncRNA MEG3 and its antitumor effects in human hepatoma cells. Int J Oncol 48(1):421–429. doi:10.3892/ijo.2015.3248 PubMed

22.

Zhou Y, Zhang X, Klibanski A (2012) MEG3 noncoding RNA: a tumor suppressor. J Mol Endocrinol 48(3):R45–R53. doi:10.1530/JME-12-0008 CrossRefPubMedPubMedCentral

23.

Liu YL, Yang HP, Zhou XD, Gong L, Tang CL, Wang HJ (2011) The hypomethylation agent bisdemethoxycurcumin acts on the WIF-1 promoter, inhibits the canonical Wnt pathway and induces apoptosis in human non-small-cell lung cancer. Curr Cancer Drug Targets 11(9):1098–1110CrossRefPubMed

24.

Zamani M, Sadeghizadeh M, Behmanesh M, Najafi F (2015) Dendrosomal curcumin increases expression of the long non-coding RNA gene MEG3 via up-regulation of epi-miRs in hepatocellular cancer. Phytomed Int J Phytother Phytopharmacol 22(10):961–967. doi:10.1016/j.phymed.2015.05.071 CrossRef

Title: Curcumin suppresses cisplatin resistance development partly via modulating extracellular vesicle-mediated transfer of MEG3 and miR-214 in ovarian cancer
Authors: Jing Zhang
Jinyu Liu
Xinyan Xu
Li Li
Publication date: 01-03-2017
Publisher: Springer Berlin Heidelberg
Published in: Cancer Chemotherapy and Pharmacology / Issue 3/2017
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-017-3238-4

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 3/2017

Phase 1 study of new formulation of patritumab (U3-1287) Process 2, a fully human anti-HER3 monoclonal antibody in combination with erlotinib in Japanese patients with advanced non-small cell lung cancer

Artemisinin and its derivatives in cancer therapy: status of progress, mechanism of action, and future perspectives

Concise review of the management of iatrogenic emesis using cannabinoids: emphasis on nabilone for chemotherapy-induced nausea and vomiting

NC-6004 Phase I study in combination with gemcitabine for advanced solid tumors and population PK/PD analysis

Evaluation of gefitinib efficacy according to body mass index, body surface area, and body weight in patients with EGFR-mutated advanced non-small cell lung cancer

Positive relationship between subsequent chemotherapy and overall survival in pancreatic cancer: meta-analysis of postprogression survival for first-line chemotherapy

Keynote webinar | Spotlight on antibody–drug conjugates in cancer