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Anticancer evaluation of a novel dithiocarbamate hybrid as the tubulin polymerization inhibitor

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Summary

Novel quinoline-dithiocarbamate hybrids were synthesized and designed by the molecular hybridization strategy. All these derivatives were evaluated for their antiproliferative activity against three selected cancer cell lines (MGC-803, HepG-2 and PC-3). Among them, compound 10c displayed the best antiproliferative activity against PC-3 cells with an IC50 value of 0.43 μM. Celluar mechanisms investigated that compound 10c could inhibit the migration against PC-3 cells by regulation the expression levels of E-cadherin and N-cadherin. Compound 10c induced morphological changes of PC-3 cells and regulated apoptosis-related proteins (Bcl-2, Bax and Cleaved-Parp). In addition, compound 10c inhibited tubulin polymerization in vitro with an IC50 value of 4.02 μM. Importantly, compound 10c inhibited the growth of PC-3 cells in vivo with the low toxicity toward mice. These results suggested that compound 10c might be an antitumor agent with potential for treating prostate cancer.

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References

  1. Nainwal LM, Tasneem S, Akhtar W, Verma G, Khan MF, Parvez S, Shaquiquzzaman M, Akhter M, Alam MM (2019) Green recipes to quinoline: a review. Eur J Med Chem 164:121–170

    Article  CAS  Google Scholar 

  2. Afzal O, Kumar S, Haider MR, Ali MR, Kumar R, Jaggi M, Bawa S (2015) A review on anticancer potential of bioactive heterocycle quinoline. Eur J Med Chem 97:871–910

    Article  CAS  Google Scholar 

  3. Li S, Hu L, Li J, Zhu J, Zeng F, Huang Q, Qiu L, Du R, Cao R (2019) Design, synthesis, structure-activity relationships and mechanism of action of new quinoline derivatives as potential antitumor agents. Eur J Med Chem 162:666–678

    Article  CAS  Google Scholar 

  4. Lee HY, Chang CY, Su CJ, Huang HL, Mehndiratta S, Chao YH, Hsu CM, Kumar S, Sung TY, Huang YZ, Li YH, Yang CR, Liou JP (2016) 2-(Phenylsulfonyl)quinoline N-hydroxyacrylamides as potent anticancer agents inhibiting histone deacetylase. Eur J Med Chem 122:92–101

    Article  CAS  Google Scholar 

  5. Li W, Shuai W, Sun H, Xu F, Bi Y, Xu J, Ma C, Yao H, Zhu Z, Xu S (2019) Design, synthesis and biological evaluation of quinoline-indole derivatives as anti-tubulin agents targeting the colchicine binding site. Eur J Med Chem 163:428–442

    Article  CAS  Google Scholar 

  6. Buac D, Schmitt S, Ventro G, Kona FR, Dou QP (2012) Dithiocarbamate-based coordination compounds as potent proteasome inhibitors in human cancer cells. Mini Rev Med Chem 12:1193–1201

    Article  CAS  Google Scholar 

  7. Laskar S, Sánchez-Sánchez L, Flores SM, López-Muñoz H, Escobar-Sánchez ML, López-Ortiz M, Hernández-Rodríguez M, Regla I (2018) Identification of (1S,4S)-2,5-diazabicyclo[2.2.1]heptane-dithiocarbamate-nitrostyrene hybrid as potent antiproliferative and apoptotic inducing agent against cervical cancer cell lines. Eur J Med Chem 146:621–635

    Article  CAS  Google Scholar 

  8. Yang CR, Peng B, Cao SL, Ren TT, Jiang W, Wang FC, Li YS, Wang G, Li Z, Xu S, Liao J, Wang H, Li J, Xu X (2018) Synthesis, cytotoxic evaluation and target identification of thieno[2,3-d]pyrimidine derivatives with a dithiocarbamate side chain at C2 position. Eur J Med Chem 154:324–340

    Article  CAS  Google Scholar 

  9. Li RD, Wang HL, Li YB, Wang ZQ, Wang X, Wang YT, Ge ZM, Li RT (2015) Discovery and optimization of novel dual dithiocarbamates as potent anticancer agents. Eur J Med Chem 93:381–391

    Article  CAS  Google Scholar 

  10. Kerru N, Singh P, Koorbanally N, Raj R, Kumar V (2017) Recent advances (2015–2016) in anticancer hybrids. Eur J Med Chem 142:179–212

    Article  CAS  Google Scholar 

  11. Guilford P, Hopkins J, Harraway J, McLeod M, McLeod N, Harawira P, Taite H, Scoular R, Miller A, Reeve AE (1998) E-cadherin germline mutations in familial gastric cancer. Nature 392:402

    Article  CAS  Google Scholar 

  12. Karen MH, David YSC, Eric RF (2002) The SLUG zinc-finger protein represses E-cadherin in breast cancer. Cancer Res 62:1613–1618

    Google Scholar 

  13. Hassan M, Watari H, AbuAlmaaty A, Ohba Y, Sakuragi N (2014) Apoptosis and molecular targeting therapy in cancer. Biomed Res Int 2014:150845–150845

    PubMed  PubMed Central  Google Scholar 

  14. Matsuura K, Canfield K, Feng W, Kurokawa M (2016) Metabolic regulation of apoptosis in Cancer. Int Rev Cell Mol Bio 327:43–87

    Article  CAS  Google Scholar 

  15. La Regina G, Bai R, Rensen WM, Di CE, Coluccia A, Piscitelli F, Famiglini V, Reggio A, Nalli M, Pelliccia S, Da PE, Costa B, Granata I, Porta A, Maresca B, Soriani A, Iannitto ML, Santoni A, Li J, Miranda CM, Chen F, Ni Y, Brancale A, Dondio G, Vultaggio S, Varasi M, Mercurio C, Martini C, Hamel E, Lavia P, Novellino E, Silvestri R (2013) Toward highly potent cancer agents by modulating the C-2 group of the arylthioindole class of tubulin polymerization inhibitors. J Med Chem 56:123–149

    Article  Google Scholar 

  16. Zhao W, Bai JK, Li HM, Chen T, Tang YJ (2015) Tubulin structure-based drug design for the development of novel 4β-sulfur-substituted podophyllum tubulin inhibitors with anti-tumor activity. Sci Rep 5:10172–10172

    Article  CAS  Google Scholar 

  17. Reddy MVR, Akula B, Cosenza SC, Lee CM, Mallireddigari MR, Pallela VR, Subbaiah DRCV, Udofa A, Reddy EP (2012) (Z)-1-aryl-3-arylamino-2-propen-1-ones, highly active stimulators of tubulin polymerization: synthesis, structure-activity relationship (SAR), tubulin polymerization, and cell growth inhibition studies. J Med Chem 55:5174–5187

    Article  CAS  Google Scholar 

  18. Thomas E, Gopalakrishnan V, Hegde M, Kumar S, Karki SS, Raghavan SC, Choudhary BA (2016) Novel resveratrol based tubulin inhibitor induces mitotic arrest and activates apoptosis in Cancer cells. Sci Rep 6:34653–34653

    Article  CAS  Google Scholar 

  19. Yang F, Song L, Wang H, Wang J, Xu Z, Xing N (2015) Combination of quercetin and 2-Methoxyestradiol enhances inhibition of human prostate Cancer LNCaP and PC-3 cells xenograft tumor growth. PLoS One 10:e0128277–e0128277

    Article  Google Scholar 

  20. Friedemann M, Nacke B, Hagelgans A, Jandeck C, Bechmann N, Ullrich M, Belter B, Neuber C, Sukocheva O, Pietzsch J, Menschikowski M (2018) Diverse effects of phospholipase A2 receptor expression on LNCaP and PC-3 prostate cancer cell growth in vitro and in vivo. Oncotarget 9:35983–35996

    Article  Google Scholar 

  21. Lee ST, Wong PF, He H, Hooper JD, Mustafa MR (2013) Alpha-tomatine attenuation of in vivo growth of subcutaneous and orthotopic xenograft tumors of human prostate carcinoma PC-3 cells is accompanied by inactivation of nuclear factor-kappa B signaling. PLoS One 8:e57708–e57708

    Article  CAS  Google Scholar 

  22. George TG, Endeshaw MM, Morgan RE, Mahasenan KV, Delfín DA, Mukherjee MS, Yakovich AJ, Fotie J, Li C, Werbovetz KA (2007) Synthesis, biological evaluation, and molecular modeling of 3,5-substituted-N1-phenyl-N4,N4-di-n-butylsulfanilamides as antikinetoplastid antimicrotubule agents. Bioorg Med Chem 15:6071–6079

    Article  CAS  Google Scholar 

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Acknowledgments

So thanks the supports from The 4th affiliated hospital of CMU.

Funding

This work was supported by The 4th affiliated hospital of CMU.

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Authors and Affiliations

  1. Department of Urology, The Fourth Affiliated Hospital of China Medical University, Shenyang, 110032, China

    Jia Liu, Dongwei Xue, Xingwang Zhu, Liu Yu, Minghuan Mao & Yili Liu

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  1. Jia Liu
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  2. Dongwei Xue
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  3. Xingwang Zhu
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  4. Liu Yu
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  5. Minghuan Mao
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  6. Yili Liu
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Contributions

Jia Liu., Dongwei Xue., Xingwang Zhu., Liu Yu., Minghuan Mao and Yili Liu performed the design work and experiments. Jia Liu and Yili Liu witten the paper. All authors read and approved the final manuscript.

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Correspondence to Yili Liu.

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The authors declare that they have no conflict of interest.

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This article does not contain any studies with human participants performed by any of the authors. All applicable guidelines for the care and use of animals were followed by the 4th affiliated hospital of CMU (Shenyang, China).

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Informed consent was obtained from all individual participants included in the study.

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Liu, J., Xue, D., Zhu, X. et al. Anticancer evaluation of a novel dithiocarbamate hybrid as the tubulin polymerization inhibitor. Invest New Drugs 38, 525–532 (2020). https://doi.org/10.1007/s10637-019-00799-z

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  • DOI: https://doi.org/10.1007/s10637-019-00799-z

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