Anti-Tumor Effects of Lignans-1 on Human Gastric Cancer SGC-7901 Cells <i>in Vitro</i>_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 QIYing-wen ¹ , PENGChao ¹ , XIAYa-mu ² , XUKun ¹ , WANGZhi-wei ¹ ,  CHAIChen ¹

1. 3rd General Surgery, The First Hospital of Lanzhou University, Lanzhou 730000, Gansu Province, China;
2. College of Chemical Engineering, Qingdao University of Science & Technology, Qingdao 266000, Shandong Province, China;

Corresponding author：

CHAIChen, Email: chasechai@126.com

Keywords：

Lignans; Antineoplastic activity; Drug evaluation; Cell apoptosis

DOI：

10.7507/1007-9424.20160309

Video：

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Objective To investigate the mechanism of lignans-1inhibiting the proliferation of human gastric cancer cell line SGC-7901. Methods The morphological changes of the cells were observed by the inverted phase contrast microscope. The cell surviving ratio was determined by methylthiazoly tetrazolium (MTT) assay after lignans-1 added to the cells at different concentrations on human gastric cancer SGC-7901 cell line in vitro, and half maximal (50%) inhibitory concentration (IC50) values were calculated. The cell cycle phase distribution and apoptosis were measured by flow cytometry. The expressions of apoptosis associated proteins of Caspase3, Bcl-2 and Bax were determined by Western blot. Results Morphological examination showed that lignans-1 could destroy the SGC-7901 cells with the increasing concentration of lignans-1. The inhibitory effect of lignans-1 on SGC-7901 cell was associated with time-and dose-dependent manner at the different concentration (2.5-20 μg/mL), P < 0.05. The IC50 of lignans-1 on the SGC-7901 cells was 4.19 μg/mL. The rate of the apoptosis cells and G₂/M phase cells raised significantly after 48 hours' treatment with lignans-1, as same as the expression of Caspase3 and Bax (P < 0.05). G₀/G₁ phase cells and Bcl-2 decreased significantly with the increasing concentration of lignans-1 (P < 0.05). Conclusions The lignans-1 could inhibit the proliferation of SGC-7901 cells and induce apoptosis by arresting cells at G2/M phase in vitro. The mechanism is associated with activation of Caspase3 and Bax and inhibition of Bcl-2.

Citation： QI Ying-wen, PENG Chao, XIA Ya-mu, XU Kun, WANG Zhi-wei, CHAI Chen. Anti-Tumor Effects of Lignans-1 on Human Gastric Cancer SGC-7901 Cells in Vitro. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2016, 23(10): 1204-1208. doi: 10.7507/1007-9424.20160309 Copy

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1. 国家药典委员会. 中华人民共和国药典. 一部. 北京:化学工业出版社,2010:66-67.
2. Umehara K, Nakamura M, Miyase T, et al. Studies on differentiation inducers. Ⅵ. Lignan derivatives from Arctium fructus. Chem Pharm Bull (Tokyo), 1996, 44(12):2300-2334.
3. Xia Y, Dai X, Liu H, et al. First total synthesis of Boehmenan. J Chem Sci, 2014, 126(3):813-820.
4. Ferro A, Peleteiro B, Malvezzi M, et al. Worldwide trends in gastric cancer mortality (1980-2011), with predictions to 2015, and incidence by subtype. Eur J Cancer, 2014, 50(7):1330-1344.
5. Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide:sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer, 2015, 136(5):E359-E386.
6. 黎军和, 熊建萍. 胃癌分子靶向治疗研究新进展. 中国肿瘤临床,2015,42(23):1118-1123.
7. Lee KH, Xiao ZY. Lignans in treatment of cancer and other diseases†. Phytochem Rev, 2003, 2(3):341-362.
8. Awale S, Lu J, Kalauni SK, et al. Identification of arctigenin as an antitumor agent having the ability to eliminate the tolerance of cancer cells to nutrient starvation. Cancer Res, 2006, 66(3):1751-1757.
9. 孙成宏, 赖新强, 张丽, 等.牛蒡子苷元对炎性刺激剂PMA/ionomycin诱导淋巴细胞活化的抑制作用. 药学学报,2014, 49(4):482-489.
10. Huang K, Li LA, Meng YG, et al. Arctigenin promotes apoptosis in ovarian cancer cells via the iNOS/NO/STAT3/survivin signalling. Basic Clin Pharmacol Toxicol,2014, 115(6):507-511.
11. Chang CZ, Wu SC, Chang CM, et al. Arctigenin, a potent ingredient of arctium lappa L., induces endothelial nitric oxide synthase and attenuates subarachnoid hemorrhage-induced vasospasm through PI3K/Akt pathway in a rat model. Biomed Res Int, 2015, 2015:490209.
12. 浦光瑞, 刘法昱, 王博.牛蒡苷元对人口腔鳞癌裸鼠移植瘤生长及VEGF蛋白表达的影响.上海口腔医学, 2015, 24(4):400-403.
13. 秦智彬, 丁林芬, 李兰, 等. 牛蒡子化学成分的研究. 天然产物研究与开发, 2015, 27(12):2050-2055.
14. Lu Y, Suh SJ, Kwak CH, et al. Saucerneol F, a new lignan, inhibits iNOS expression via MAPKs, NF-kappaB and AP-1 inactivation in LPS-induced RAW264.7 cells. Int Immunopharmacol, 2012, 12(1):175-181.
15. Chen GR, Li HF, Dou DQ, et al. (-)-Arctigenin as a lead compound for anticancer agent. Nat Prod Res, 2013, 27(23):2251-2255.
16. Yang Y, Hu Z, Luo Z, et al. A new sesquilignan glucoside from Uraria sinensis. Molecules, 2014, 19(1):1178-1188.
17. Cheng WH, Shang H, Niu C, et al. Synthesis and evaluation of new podophyllotoxin derivatives with in vitro anticancer activity. Molecules, 2015, 20(7):12266-12279.
18. Bakar F, Caglayan MG, Onur F, et al. Gold nanoparticle-lignan complexes inhibited MCF-7 cell proliferation in vitro:a novel conjugation for cancer therapy. Anticancer Agents Med Chem, 2015, 15(3):336-344.
19. Teponno RB, Kusari S, Spiteller M. Recent advances in research on lignans and neolignans. Nat Prod Rep, 2016 May 9.[Epub ahead of print].
20. Wang Y, Xia C, Zhang W, et al. Synthesis and biological evaluation of novel lignan glycosides as anticancer agents. Chem Biol Drug Des, 2016 May 10.[Epub ahead of print].
21. Thompson CB. Apoptosis in the pathogenesis and treatment of disease. Science, 1995, 267(5203):1456-1462.
22. Wu H, Che X, Zheng Q, et al. Caspases:a molecular switch node in the crosstalk between autophagy and apoptosis. Int J Biol Sci, 2014, 10(9):1072-1083.
23. Springer JE, Nottingham SA, McEwen ML, et al. Caspase-3 apoptotic signaling following injury to the central nervous system. Clin Chem Lab Med, 2001, 39(4):299-307.
24. Stennicke HR, Jürgensmeier JM, Shin H, et al. Pro-caspase-3 is a major physiologic target of caspase-8. J Biol Chem, 1998, 273(42):27084-27090.
25. Isobe N, Onodera H, Mori A, et al. Caspase-3 expression in human gastric carcinoma and its clinical significance. Oncology, 2004, 66(3):201-209.
26. Shamas-Din A, Kale J, Leber B, et al. Mechanisms of action of Bcl-2 family proteins. Cold Spring Harb Perspect Biol, 2013, 5(4):a008714.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Anti-Tumor Effects of Lignans-1 on Human Gastric Cancer SGC-7901 Cells in Vitro

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