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

Journal Article · Tue Jan 15 04:00:00 EST 2019 · Medicinal Chemistry Research (Print)

DOI:https://doi.org/10.1007/S00044-018-2257-Y· OSTI ID:22936220

Li, Xuejiao ^[1]; Sun, Jiachen ^[2]; Li, Xia ^[1]; Dai, Yujie ^[3]; Zhao, Chengcheng ^[1]; Man, Shuli ^[3]; Wang, Ying ^[4]; Gao, Wenyuan ^[1]

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1. Tianjin University, Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology (China)
2. Tianjin University of Commerce, School of Biotechnology and Food Science (China)
3. Tianjin University of Science & Technology, Tianjin Key Laboratory of Industry Microbiology, College of Biotechnology (China)
4. Tianjin University of Traditional Chinese Medicine, Tianjin Key Laboratory of Chemistry and Analysis of Chinese Materia Medica (China)

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.

• OSTI ID: 22936220
• Journal Information: Medicinal Chemistry Research (Print), Journal Name: Medicinal Chemistry Research (Print) Journal Issue: 1 Vol. 28; ISSN 1054-2523
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ACETATES
APOPTOSIS
CELL CYCLE
CELL PROLIFERATION
LUNGS
METASTASES
NEOPLASMS
POLYMERASE CHAIN REACTION
PROTEINS
SAPONINS