Saponin from Tupistra chinensis Bak Inhibits NF-κB Signaling in Sarcoma S-180 Cell Mouse Xenografts

Abstract

This study examined the effect of saponins from Tupistra chinensis Bak (STCB) on the growth of sarcoma S-180 cells in vitro and in mouse xenografts as well as the underlying mechanisms. Cell proliferation was assessed by MTT assay. Cell cycle distribution was determined by flow cytometry. Sarcoma S-180 tumor-bearing mice were treated with different doses of STCB with 10 μg/mL 5-fluorouracil (5-Fu) as a positive control. The activity of nuclear factor (NF)-κB was detected by gel mobility shift assay. The mRNA level of NF-κB was determined by real-time quantitative RT-PCR. The results showed that in vitro STCB inhibited the growth of S-180 cells in a concentration-dependent manner, which was accompanied by cell cycle arrest at S-phase. In vivo STCB significantly inhibited the growth of S-180 tumor mouse xenografts in a dose-dependent manner with apparent induction of cell apoptosis. Moreover, STCB inhibited the activity of NF-κB p65 and reduced the expression of NF-κB p65 mRNA in mouse xenografts. It was concluded that STCB inhibits the proliferation and cell cycle progression of S-180 cells by suppressing NF-κB signaling in mouse xenografts. Our findings suggest STCB is a promising agent for the treatment of sarcoma.

Keywords

Tupistra chinensis Bak / S-180 cells / proliferation / nuclear factor-κB

References

[1] HanMX, ChenHY. Research progress on status quo of psychological distress in malignant tumor patients and its related factors. J EBN (Chinese), 2016, 2(1): 1-6

[2] YangQC, ZhanYC, HuML, et al.. Study on pharmacognosy characteristics of Chinese herbal medicine. J Shanxi U T (Chinese), 2016, 1(2): 76-81

[3] TangCZ, YuL, LiuJQ, et al.. Advances in studies on physiological active substances and their pharmacological actions of open arrow. J Henan Normal University (Chinese), 2016, 2(2): 114-118

[4] HuangW, HeML, JiangMQ, et al.. Total saponins of Tupistra chinensis induces apoptosis in A549 cells. Neoplasma, 2012, 59(6): 613-621

[5] CaiJ, QiHM, LiuBW, et al.. Saponin from Tupistra chinensis Baker inhibits mouse sarcoma S-180 cell proliferation in vitro and implanted solid tumor growth in mice. Nan Fang Yi Ke Da Xue Xue Bao (Chinese), 2007, 27(1): 188-190

[6] XieJY, GuoW, HuML, et al.. Study on apoptosis of tumor cell induced by saponin of Chinese herb. Pharmacol Clin, 2014, 3(2): 82-86

[7] ManiatiE. Crosstalk between the canonical NFkappaB and Notch signaling pathways inhibits Ppargamma expression and promotes pancreatic cancer progression in mice. J Clin Invest, 2011, 12(1): 4685-4699

[8] LvKJ. Expression of NF-κB and VEGF in nonsmall cell lung cancer and its relationships with tumor angiogenesis. Chin J Histochem Cytochem (Chinese), 2013, 2(2): 59-62

[9] XieJ, ZhangDD, LiYZ, et al.. Study on apoptosis of tumor cells induced by Tupistra chinensis Bak. Chin Med Pharmacol Clin (Chinese), 2014, 30(3): 82-86

[10] ChengY, ZhangL. Progress in research on antitumor mechanism and drug of Chinese Medicine. China Pharmaceut (Chinese), 2013, 17(3): 103-110

[11] MeijermanI, BeijnenJH, SchellensJHM. Herb-drug interactions in oncology: focus on mechanisms of induction. Oncologist, 2006, 11(7): 742-752

[12] WangJL. Computer aided virtual screening of active ingredients of antineoplastic Chinese medicine. Ocean Univer China (Chinese), 2011, 9: 10-11

[13] PrasadS. NF-kappaB and cancer: how intimate is this relationship. Mol Cell Biochem, 2010, 33(6): 25-37

[14] MeiyantoE, PutriDD, SusidartiRA, et al.. Curcumin and its analogues (PGV-0 and PGV-1) enhance sensitivity of resistant MCF-7 cells to doxorubicin through inhibition of HER2 and NF-kB activation. Asian Рас J Cancer Prev, 2014, 15(1): 179-184

[15] OrrWS, DenboJW, SaabKR, et al.. Liposomeencapsulated curcumin suppresses neuroblastoma growth through nuclear factor-kappa B inhibition. Surgery, 2012, 159(2): 736-744

[16] MaramponF. Nerve growth factor regulation of cyclin D1 in PC12 cells through a p21RAS extracellular signal-regulated kinase pathway requires cooperative interactions between Spl and nuclear factor-kappaB. Mol Biol Cell, 2008, 19(2): 2566-2578

[17] GaoLW. Effect of astragalus extract on related protein expression of NF-κB signal pathway in AD rats. Occupation Health (Chinese), 2017, 15(1): 44-47

[18] ShinEM, HayHS, LeeMH, et al.. DEAD-box helicase DP 103 defines metastatic potential of human breast cancers. J Clin Invest, 2014, 124(9): 3807-3824

[19] DavoudiZ, AkbarzadehA, RahmatiyamchiM, et al.. Molecular target therapy of AKT and NF-kB signaling pathways and multidrug resistance by specific cell penetrating inhibitor peptides in HL-60 cells. Asian Рас J Cancer Prev, 2014, 15(10): 4353-4358

[20] ZhangLY, SunHB. A randomized parallel controlled study on the effects of Qi supplementing Yang Yang Decoction on TNF-alpha and NF-kB in rats with allergic rhinitis. Chin J Pract Chin Intern Med (Chinese), 2016, 12(3): 95-98