IMP-1 inhibits renal cell carcinoma 786-O cell growth by targeting EphrinB2 signaling pathway

Authors

  • Juan Liu The Weapons Industry of institutes of health, Xi’an, Shaanxi, China
  • Hong Shi The Airforce Military Medical University. Tangdu Hospital, Xi’an, Shaanxi, China https://orcid.org/0000-0002-3491-6127

DOI:

https://doi.org/10.1590/s2175-97902023e22102%20%20

Keywords:

Renal cell carcinoma, IMP-1, EphrinB2, Cell cycle, Cell apoptosis.

Abstract

EphrinB2 plays a critical role in tumor growth. In this study, we studied the antitumor activity of imperatorin derivative IMP-1 in renal cell carcinoma (RCC) by regulating EphrinB2 pathway.. Results showed that IMP-1 inhibited the proliferation of 786-O cells in a dose- and time-dependent manner. More importantly, knockdown and transfection of EphrinB2 altered the inhibitory effect of IMP-1 on the activity of 786-O cells. IMP-1 arrested 786-O cell cycle at G0/G1 phase by decreasing the expression of cyclin D1 and cyclin E. Moreover, IMP-1 regulated Bcl-2 family proteins’ expression, thus inducing apoptosis of 786-O cells. IMP-1 down-regulated the expression of EphrinB2, Syntenin1 and PICK1. Then, IMP-1 decreased the phosphorylation of Erk1/2 and AKT. In all, IMP-1 could regulate the EphrinB2 pathway in order to inhibit 786-O cell growth by arresting the cell cycle at G0/G1 phase and inducing cell apoptosis. Thus, IMP-1 may present as a potential strategy for RCC treatment.

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References

Barata PC, Rini BI. Treatment of renal cell carcinoma: Current status and future directions. CA Cancer J Clin. 2017;67(6):507-524.

Bonelli M, La Monica S, Fumarola C, Alfieri R. Multiple effects of cdk4/6 inhibition in cancer: From cell cycle arrest to immunomodulation. Biochem Pharmacol. 2019;170:113676.

Curtis SA, Cohen JV, Kluger HM. Evolving immunotherapy approaches for renal cell carcinoma. Curr Oncol Rep. 2016;18(9):57.

Dravis C, Henkemeyer M. Ephrin-b reverse signaling controls septation events at the embryonic midline through separate tyrosine phosphorylation-independent signaling avenues. Dev Biol. 2011;355(1):138-151.

Elmore S. Apoptosis: A review of programmed cell death. Toxicol Pathol. 2007;35(4):495-516.

Genander M, Frisen J. Ephrins and eph receptors in stem cells and cancer. Curr Opin Cell Biol. 2010;22(5):611-616.

Germain S, Eichmann A. Vegf and ephrin-b2: A bloody duo. Nat Med. 2010;16(7):752-754.

Gray RE, Harris GT. Renal cell carcinoma: Diagnosis and management. Am Fam Physician. 2019;99(3):179-184.

He HZ, Wang C, Wang T, Zhou N, Wen ZY, Wang SC, et al. Synthesis, characterization and biological evaluation of fluorescent biphenyl-furocoumarin derivatives. Dyes Pigm. 2015;113:174-180.

Kanska J, Zakhour M, Taylor-Harding B, Karlan BY, Wiedemeyer WR. Cyclin e as a potential therapeutic target in high grade serous ovarian cancer. Gynecol Oncol. 2016;143(1):152-158.

Kozioł E, Skalicka-Woźniak K. Imperatorin-pharmacological meaning and analytical clues: Profound investigation. Phytochem Rev. 2016;15:627-649.

Li J, Wang D, Liu J, Qin Y, Huang L, Zeng Q, et al. Rce1 expression in renal cell carcinoma and its regulatory effect on 786-o cell apoptosis through endoplasmic reticulum stress. Acta Biochim Biophys Sin. 2017;49(3):254-261.

Liu F, Wan L, Zou H, Pan Z, Zhou W, Lu X. Prmt7 promotes the growth of renal cell carcinoma through modulating the β-catenin/c-myc axis. Int J Biochem Cell Biol. 2020;120:105686.

Ma W, Zhu M, Zhang D, Yang L, Yang TF, Li X, et al. Berberine inhibits the proliferation and migration of breast cancer zr-75-30 cells by targeting ephrin-b2. Phytomedicine. 2017a;25:45-51.

Ma WN, Zhu M, Yang L, Yang TF, Zhang YM. Synergistic effect of tpd7 and berberine against leukemia jurkat cell growth through regulating ephrin-b2 signaling. Phytother Res. 2017b;31(9):1392-1399.

Malumbres M, Barbacid M. Cell cycle, cdks and cancer: A changing paradigm. Nat Rev Cancer. 2009;9(3):153-166.

Messeha SS, Zarmouh NO, Mendonca P, Alwagdani H, Cotton C, Soliman KFA. Effects of gossypol on apoptosis-related gene expression in racially distinct triple-negative breast cancer cells. Oncol Rep. 2019;42(2):467-478.

Messeha SS, Zarmouh NO, Asiri A, Soliman KFA. Rosmarinic acid-induced apoptosis and cell cycle arrest in triple-negative breast cancer cells. Eur J Pharmacol. 2020;885:173419.

Poliakov A, Cotrina M, Wilkinson DG. Diverse roles of eph receptors and ephrins in the regulation of cell migration and tissue assembly. Dev Cell. 2004;7(4):465-480.

Posadas EM, Limvorasak S, Figlin RA. Targeted therapies for renal cell carcinoma. Nat Rev Nephrol. 2017;13(8):496-511.

Warren CFA, Wong-Brown MW, Bowden NA. Bcl-2 family isoforms in apoptosis and cancer. Cell Death Dis. 2019;10(3):177.

Wenzel ES, Singh ATK. Cell-cycle checkpoints and aneuploidy on the path to cancer. In Vivo. 2018;32(1):1-5.

Wu KC, Chen YH, Cheng KS, Kuo YH, Yang CT, Wong KL, et al. Suppression of voltage-gated na(+) channels and neuronal excitability by imperatorin. Eur J Pharmacol. 2013;721(1-3):49-55.

Zhang BB, Wang DG, Guo FF, Xuan C. Mitochondrial membrane potential and reactive oxygen species in cancer stem cells. Fam Cancer. 2015;14(1):19-23.

Zhang YM, Zhan YZ, Zhang DD, Dai BL, Ma WN, Qi JP, et al. Eupolyphaga sinensis walker displays inhibition on hepatocellular carcinoma through regulating cell growth and metastasis signaling. Sci Rep. 2014;4:5518.

Zhu M, Cui Y, Yang L, Yang T, Wang H, Zhang D, et al. Ephrin type-b receptor 4 affinity chromatography: An effective and rapid method studying the active compounds targeting ephrin type-b receptor 4. J Chromatogr A. 2018;1586:82-90.

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Published

2023-06-22

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Original Article

How to Cite

IMP-1 inhibits renal cell carcinoma 786-O cell growth by targeting EphrinB2 signaling pathway. (2023). Brazilian Journal of Pharmaceutical Sciences, 59, e22102. https://doi.org/10.1590/s2175-97902023e22102