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Dioscin-6’-O-acetate impairs migration of lung cancer cells through attenuations of MMP-2 and MMP-9 via NF-κB suppression
- Source :
- Medicinal Chemistry Research. 28:1-12
- Publication Year :
- 2018
- Publisher :
- Springer Science and Business Media LLC, 2018.
-
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.
- Subjects :
- biology
medicine.diagnostic_test
010405 organic chemistry
Chemistry
Organic Chemistry
Caspase 3
NF-κB
Matrix metalloproteinase
medicine.disease
01 natural sciences
0104 chemical sciences
Metastasis
Proliferating cell nuclear antigen
010404 medicinal & biomolecular chemistry
chemistry.chemical_compound
Western blot
Apoptosis
medicine
biology.protein
Cancer research
General Pharmacology, Toxicology and Pharmaceutics
Lung cancer
Subjects
Details
- ISSN :
- 15548120 and 10542523
- Volume :
- 28
- Database :
- OpenAIRE
- Journal :
- Medicinal Chemistry Research
- Accession number :
- edsair.doi...........7f070e207dc410a392d32c93da8c740e