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Thiocoraline mediates drug resistance in MCF-7 cells via PI3K/Akt/BCRP signaling pathway

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Abstract

Thiocoraline, a depsipeptide bisintercalator with potent antitumor activity, was first isolated from marine actinomycete Micromonospora marina. It possesses an intense toxicity to MCF-7 cells at nanomolar concentrations in a dose-dependent manner evaluated by MTT assay and crystal violet staining. We established a human breast thiocoraline-resistant cancer subline of MCF-7/thiocoraline (MCF-7/T) to investigate the expression variation of breast cancer resistance proteins (BCRP) and its subsequent influence on drug resistance. Colony-forming assay showed that the MCF-7 cells proliferated faster than the MCF-7/T cells in vitro. Western blot analysis demonstrated that thiocoraline increased the phosphorylation of Akt. Additionally, the sensitivity of tumor cells to thiocoraline was reduced with a concurrent rise in phosphorylation level of Akt and of BCRP expression.These studies indicated that thiocoraline probably mediated the drug resistance via PI3K/Akt/BCRP signaling pathway. MK-2206 dihydrochloride, a selective phosphorylation inhibitor of Akt, significantly decreased MCF-7 cell viability under exposure to thiocoraline compared to the control. However, it was not obviously able to decrease MCF-7/T cell viability when cells were exposed to thiocoraline.

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References

  • Baz JP, Canedo LM, Puentes J, Elipe M (1997) Thiocoraline, a novel depsipeptide with antitumor activity produced by a marine Micromonospora II. Physico-chemical properties and structure determination. J Antibiot 50:738–741

    Article  Google Scholar 

  • Bleau AM, Huse JT, Holland EC (2009) The abcg2 resistance network of glioblastoma. Cell Cycle 8:2937–2945

    Article  CAS  Google Scholar 

  • Boger DL, Ichikawa S, Tse WC, Hedrick MP, ** Q (2001) Total syntheses of thiocoraline and BE-22179 and assessment of their DNA binding and biological properties. J Am Chem Soc 123:561–568

    Article  CAS  PubMed  Google Scholar 

  • Brechbuhl HM, Gould N, Kachadourian R, Riekhof WR, Voelker DR, Day BJ (2010) Glutathione transport is a unique function of the ATP-binding cassette protein ABCG2. J Biol Chem 285:16582–16587

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Camunas-Soler J, Manosas M, Frutos S, Tulla-Puche J, Albericio F, Ritort F (2015) Single-molecule kinetics and footprinting of DNA bis-intercalation: the paradigmatic case of Thiocoraline. Nucleic Acids Res 43:2767–2779

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dawson S, Malkinson JP, Paumier D, Searcey M (2007) Bisintercalator natural products with potential therapeutic applications: isolation, structure determination, synthetic and biological studies. Nat Prod Rep 24:109–126

    Article  CAS  PubMed  Google Scholar 

  • De Gooijer MC, Zhang P, Weijer R, Buil LCM, Beijnen JH, van Tellingen O (2018) The impact of P-glycoprotein and breast cancer resistance protein on the brain pharmacokinetics and pharmacodynamics of a panel of MEK inhibitors. Int J Cancer 142:381–391

    Article  CAS  PubMed  Google Scholar 

  • Engelman JA (2009) Targeting PI3K signalling in cancer: opportunities, challenges and limitations. Nat Rev Cancer 9:550–562

    Article  CAS  Google Scholar 

  • Erba E, Bergamaschi D, Ronzoni S, Faretta M, Taverna S, Bonfanti M, Catapano CV, Faircloth G, Jimeno J, D’Incalci M (1999) Mode of action of thiocoraline, a natural marine compound with anti-tumour activity. Br J Cancer 80:971–980

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Faircloth G, Jimeno J, D’Incalci M (1997) Biological activity of thiocoraline, a novel marine depsipeptide. Eur J Cancer 33:175

    Article  Google Scholar 

  • Fornari FA, Randolph JK, Yalowich JC, Ritke MK, Gewirtz DA (1994) Interference by doxorubicin with DNA unwinding in MCF-7 breast tumor cells. Mol Pharmacol 45:649–656

    CAS  PubMed  Google Scholar 

  • Gammone MA, Riccioni G, Galvano F, D’Orazio N (2016) Novel therapeutic strategies against cancer: marine-derived drugs may be the answer? Anti Cancer Agent Me 16:1549–1557

    Article  CAS  Google Scholar 

  • Gerwick WH, Moore BS (2012) Lessons from the past and charting the future of marine natural products drug discovery and chemical biology. Chem Biol 19:85–98

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Guerrero-Zotano A, Mayer IA, Arteaga CL (2016) PI3K/AKT/mTOR: role in breast cancer progression, drug resistance, and treatment. Cancer Metast Rev 35:515–524

    Article  CAS  Google Scholar 

  • Harvey JH, Mcfadden M, Andrews WG, Byrne PJ, Ahlgren JD, Woolley PV (1985) Phase I study of echinomycin administered on an intermittent bolus schedule. Cancer Treat Rep 69:1365–1368

    CAS  PubMed  Google Scholar 

  • Hong YB, Kang HJ, Kwon SY, Kim HJ, Kwon KY, Cho CH, Lee JM, Kallakury BV, Bae I (2010) Nuclear factor (erythroid-derived 2)-like 2 regulates drug resistance in pancreatic cancer cells. Pancreas 39:463–472

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Imai Y, Yoshimori M, Fukuda K, Yamagishi H, Ueda Y (2012) The PI3K/akt inhibitor ly294002 reverses bcrp-mediated drug resistance, without affecting bcrp translocation. Oncol Rep 27:1703

    CAS  PubMed  Google Scholar 

  • Kandel R, Zhu XL, Li SQ, Rohan T (2001) Cyclin D1 protein overexpression and gene amplification in benign breast tissue and breast cancer risk. Eur J Cancer Prev 10:43–51

    Article  CAS  PubMed  Google Scholar 

  • Kong D, Park EJ, Stephen AG, Calvani M, Cardellina JH, Monks A, Fisher RJ, Shoemaker RH, Melillo G (2005) Echinomycin, a small-molecule inhibitor of hypoxia-inducible factor-1 DNA-binding activity. Cancer Res 65:9047–9055

    Article  CAS  PubMed  Google Scholar 

  • Kruh GD (2003) Introduction to resistance to anticancer agents. Oncogene 22:7262–7264

    Article  CAS  PubMed  Google Scholar 

  • Momparler RL, Karon M, Siegel SE, Avila F (1976) Effect of adriamycin on DNA, RNA, and protein synthesis in cell-free systems and intact cells. Cancer Res 36:2891–2895

    CAS  PubMed  Google Scholar 

  • Nakanishi T, Ross DD (2012) Breast cancer resistance protein (BCRP/ABCG2): its role in multidrug resistance and regulation of its gene expression. Chin J Cancer 31:73–99

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Negri A, Marco E, García-Hernández V, Domingo A, Llamas-Saiz AL, Porto-Sandá S, Riguera R, Laine W, David-Cordonnier M, Bailly C, García-Fernández LF, Vaquero JJ, Gago F (2007) Antitumor activity, X-ray crystal structure, and DNA binding properties of thiocoraline A, a natural bisintercalating thiodepsipeptide. J Med Chem 50:3322–3333

    Article  CAS  PubMed  Google Scholar 

  • Perez BJ, Cañedo LM, Fernández Puentes JL, Silva Elipe MV (1997) Thiocoraline, a novel depsipeptide with antitumor activity produced by a marine Micromonospora. II. Physico-chemical properties and structure determination. J Antibiot 50:738–741

    Article  Google Scholar 

  • Posch C, Moslehi H, Feeney L, Green GA, Ebaee A, Feichtenschlager V, Chong K, Peng L, Dimon MT, Phillips T, Daud AI, McCalmont TH, LeBoit PE, Ortiz-Urda S (2013) Combined targeting of MEK and PI3K/mTOR effector pathways is necessary to effectively inhibit NRAS mutant melanoma in vitro and in vivo. Proc Natl Acad Sci USA 110:4015–4020

    Article  PubMed  Google Scholar 

  • Sohn JA, Zarebczan B, Wyche TP, Bugni TS, Kunnimalaiyaan M, Jaskula-Sztul R, Chen H (2012) Thiocoraline regulates neuroendocrine phenotype and inhibits proliferation in carcinoid tumor cells. J Surg Res 172:237

    Article  Google Scholar 

  • Takada T, Suzuki H, Gotoh Y, Sugiyama Y (2005) Regulation of the cell surface expression of human bcrp/abcg2 by the phosphorylation state of Akt in polarized cells. Drug Metab Dispos 33:905–909

    Article  CAS  PubMed  Google Scholar 

  • Tandon R, Luxami V, Kaur H, Tandon N, Paul K (2017) 1,8-Naphthalimide: a potent DNA intercalator and target for cancer therapy. Chem Rec 17:956–993

    Article  CAS  PubMed  Google Scholar 

  • Tesfazghi S, Eide J, Dammalapati A, Korlesky C, Wyche TP (2013) Thiocoraline alters neuroendocrine phenotype and activates the Notch pathway in MTC-TT cell line. Cancer Med-US 2:734–743

    Article  CAS  Google Scholar 

  • Vippila MR, Ly PK, Cuny GD (2015) Synthesis and antiproliferative activity evaluation of the disulfide-containing cyclic peptide thiochondrilline C and derivatives. J Nat Prod 78:2398–2404

    Article  CAS  PubMed  Google Scholar 

  • Wang R, Zhou S, Li S (2011) Cancer therapeutic agents targeting hypoxia-inducible factor-1. Curr Med Chem 18:3168–3189

    Article  CAS  PubMed  Google Scholar 

  • Wang H, Huang F, Wang J, Wang P, Lv W, Hong L, Li S, Zhou J (2015a) The synergistic inhibition of breast cancer proliferation by combined treatment with 4EGI-1 and MK2206. Cell Cycle 14:232–242

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang Y, Liu T, Huang P, Zhao H, Zhang R, Ma B, Chen K, Huang F, Zhou X, Cui C, Liu X (2015b) A novel Golgi protein (GOLPH2)-regulated oncolytic adenovirus exhibits potent antitumor efficacy in hepatocellular carcinoma. Oncotarget 6:13564–13578

    PubMed  PubMed Central  Google Scholar 

  • Wyche TP, Dammalapati A, Cho H, Harrison AD, Kwon GS, Chen H, Bugni TS, Jaskula-Sztul R (2014) Thiocoraline activates the Notch pathway in carcinoids and reduces tumor progression in vivo. Cancer Gene Ther 21:518–525

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ying S, Zheng TT, Chen PY, Chuan-Lian XU (2013) Establishment of highly expressed cell strain of breast cancer resistance protein BCRP. J Zhejiang Sci Tech Univ 30:877–880

    Google Scholar 

  • Yue PYK, Leung HM, Li AJ, Chan TNC, Lum TS, Chung YL, Sung YH, Wong MH, Leung KSY, Zeng EY (2017) Angiosuppressive properties of marine-derived compounds—a mini review. Environ Sci Pollut R 24:8990–9001

    Article  Google Scholar 

  • Zheng TT, Pan SH, Zheng XS, Deng-Wei WU, Chuan-Lian XU (2014) Establishment of Adriamycin-resistant breast cancer Mcf-7/Adm cell line and the drug resistance feature. J Zhejiang Sci Tech Univ 31–32:216–220

    Google Scholar 

Download references

Acknowledgements

This work was financially supported by Zhejiang academician expert work station service center. Funding Number: 116129A4Q17002. We gratefully acknowledge the support from Dr. Williams Fenical group in Scripps Institution of Oceanography of University of California San Diego for supplying the compound thiocoraline.

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  1. ** ** and Yujia Zhao have contributed equally to this work.

Authors and Affiliations

  1. College of Life Sciences, Zhejiang Sci-Tech University, **asha Higher Education Zone, Hangzhou, 310018, Zhejiang Province, China

    ** **, Yujia Zhao, Wan Guo, Bingrong Wang, Yigang Wang, **nyuan Liu & Chuanlian Xu

  2. State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China

    **nyuan Liu

  3. **nyuan Institute of Medicine and Biotechnology, College of Life Sciences, Zhejiang Sci-Tech University, No. 2 Road **asha District, Hangzhou, 310018, China

    ** **, Yujia Zhao, Wan Guo, Bingrong Wang & Chuanlian Xu

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**, J., Zhao, Y., Guo, W. et al. Thiocoraline mediates drug resistance in MCF-7 cells via PI3K/Akt/BCRP signaling pathway. Cytotechnology 71, 401–409 (2019). https://doi.org/10.1007/s10616-019-00301-w

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