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Medicinal Chemistry Research

, Volume 28, Issue 1, pp 1–12 | Cite as

Dioscin-6’-O-acetate impairs migration of lung cancer cells through attenuations of MMP-2 and MMP-9 via NF-κB suppression

  • Xuejiao Li
  • Jiachen Sun
  • Xia Li
  • Yujie Dai
  • Chengcheng Zhao
  • Shuli ManEmail author
  • Ying Wang
  • Wenyuan GaoEmail author
Original Research
  • 22 Downloads

Abstract

More than 90% of the cancer-associated mortality is attributed to its metastasis. Numerous studies demonstrated that natural steroidal saponins from plants had the capacity to inhibit lung cancer metastasis. Dioscin-6’-O-acetate (DA) was a novel steroidal saponin first obtained from the rhizomes of Dioscorea althaeoides R. Knuth. Our previous study indicated that it suppressed lung cancer cell proliferation via inducing cell-cycle arrest and enhancing caspase-dependent apoptosis. Until now, there were still no reports on its anti-migration activity. In the present study, we further verified the anti-proliferation and apoptosis-inducing effects and investigated the anti-migration effects of DA on human NSCLC (NCI-H460, NCI-H1299, NCI-H520) and SCLC (NCI-H446) cells for the first time. To clarify the possible mechanisms, western blot and/or RT-PCR analysis were used. The results revealed that DA treatment increased the levels of caspase 3, 8, 9, and Bax and markedly decreased the expression of bcl-2, PCNA, MMP-2, MMP-9, and NF-κB. Docking study indicated that DA presented strong affinity with the key metastasis-related proteins, such as MMP-2, MMP-9, and NF-κB. We proposed that DA might suppress lung cancer proliferation by downregulating PCNA, induce lung cancer apoptosis via activation of caspase-dependent apoptosis pathways, and inhibit lung cancer migration possibly by targeting MMP-2/9 through NF-κB signaling suppression. The findings would provide the foundation for the clinical use of DA in future.

Keywords

Dioscin-6’-O-acetate Lung cancer Migration MMP-2 MMP-9 NF-κB 

Notes

Acknowledgements

This work was financially supported by grant NOs. 81373904, 81673535, and 81173487 from the National Natural Science Foundation of China.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

44_2018_2257_MOESM1_ESM.docx (517 kb)
Supplementary Information

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of Pharmaceutical Science and TechnologyTianjin UniversityTianjinChina
  2. 2.School of Biotechnology and Food ScienceTianjin University of CommerceTianjinChina
  3. 3.Tianjin Key Laboratory of Industry Microbiology, College of BiotechnologyTianjin University of Science & TechnologyTianjinChina
  4. 4.Tianjin Key Laboratory of Chemistry and Analysis of Chinese Materia MedicaTianjin University of Traditional Chinese MedicineTianjinChina

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