Abstract
Aim:
Fructus phyllanthi tannin fraction (PTF) from the traditional Tibetan medicine Fructus phyllanthi has been found to inhibit lung and liver carcinoma in mice. In this study we investigated the anticancer mechanisms of PTF in human lung squamous carcinoma cells in vitro.
Methods:
Human lung squamous carcinoma cell line (NCI-H1703), human large-cell lung cancer cell line (NCI-H460), human lung adenocarcinoma cell line (A549) and human fibrosarcoma cell line (HT1080) were tested. Cell viability was detected with MTT assay. Cell migration and invasion were assessed using a wound healing assay and a transwell chemotaxis chambers assay, respectively. Cell apoptosis was analyzed with flow cytometric analysis. The levels of apoptosis-related and metastasis-related proteins were detected by Western blot and immunofluorescence.
Results:
PTF dose-dependently inhibited the viability of the 3 human lung cancer cells. The IC50 values of PTF in inhibition of NCI-H1703, NCI-H460, and A549 cells were 33, 203, and 94 mg/L, respectively. PTF (15, 30, and 60 mg/L) dose-dependently induced apoptosis of NCI-H1703 cells. Treatment of NCI-H1703 and HT1080 cells with PTF significantly inhibited cell migration, and reduced the number of invasive cells through Matrigel. Furthermore, PTF dose-dependently down-regulated the expression of phosphor-ERK1/2, MMP-2 and MMP-9, up-regulated the expression of phosphor-JNK, but had no significant effect on the expression of ERK1/2 or JNK.
Conclusion:
PTF induces cell apoptosis and inhibits the migration and invasion of NCI-H1703 cells by decreasing MPPs expression through regulation of the MAPK pathway.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Gong L, Mi HJ, Zhu H, Zhou X, Yang H . P-selectin-mediated platelet activation promotes adhesion of non-small cell lung carcinoma cells on vascular endothelial cells under flow. Mol Med Rep 2012; 5: 935–42.
Dong J, Jin G, Wu C, Guo H, Zhou B, Lv J, et al. Genome-wide association study identifies a novel susceptibility locus at 12q23.1 for lung squamous cell carcinoma in han chinese. PLoS Genet 2013; 9: e1003190.
Kenfield SA, Wei EK, Stampfer MJ, Rosner BA, Colditz GA . Comparison of aspects of smoking among the four histological types of lung cancer. Tob Control 2008; 17: 198–204.
Huo XS . The expression of CD44s, CD44v6, MMP-2, MMP-9, TIMP-1 and TIMP-2 and their significance in non-small cell lung cancer [dissertation]. Tianjin: Tianjin Medical University; 2006.
Weber GF . Why does cancer therapy lack effective anti-metastasis drugs? Cancer Lett 2013; 328: 207–11.
Guo K, Kang NX, Li Y, Sun L, Gan L, Cui FJ, et al. Regulation of HSP27 on NF-kappaB pathway activation may be involved in metastatic hepatocellular carcinoma cells apoptosis. BMC Cancer 2009; 9: 100.
Reddy KB, Nabha SM, Atanaskova N . Role of MAP kinase in tumor progression and invasion. Cancer Metastasis Rev 2003; 22: 395–403.
Dhillon AS, Hagan S, Rath O, Kolch W . MAP kinase signalling pathways in cancer. Oncogene 2007; 26: 3279–90.
Xia Q, Xiao P, Wan L, Kong J . Ethnopharmacology of Phyllanthus emblica L. Zhongguo Zhong Yao Za Zhi 1997; 22: 515–8, 25, 74.
Weisburg JH, Schuck AG, Reiss SE, Wolf BJ, Fertel SR, Zuckerbraun HL, et al. Ellagic acid, a dietary polyphenol, selectively cytotoxic to HSC-2 oral carcinoma cells. Anticancer Res 2013; 33: 1829–36.
Lipińska L, Klewicka E, Sójka M . The structure, occurrence and biological activity of ellagitannins: a general review. Acta Sci Pol Technol Aliment 2014; 13: 289–99.
Yahayo W, Supabphol A, Supabphol R . Suppression of human fibrosarcoma cell metastasis by Phyllanthus emblica extract in vitro. Asian Pac J Cancer Prev 2013; 14: 6863–7.
Hu JF . Inhibitory effects of Phyllanthus emblica juice on formation of N-nitrosomorpholine in vitro and N-nitrosoproline in rat and human. Zhonghua Yu Fang Yi Xue Za Zhi 1990; 24: 132–5.
Huang QS, Lin YZ, Li HZ, Chen WQ, Qiu SL . Study on antimutangenic and antineoplastic effect of Phyllanthus emblica L. J Pract Med Techn 2007; 14: 3456–7.
Sun XF, Zhang HY, Xia Q, Zhao HJ, Wu LF, Zhang LZ, et al. HPLC-fingerprint-based quality evaluation on a Tibetan medicine Phyllanthus emblica and its tannin parts. Zhongguo Zhong Yao Za Zhi 2014; 39: 1173–8.
Ishizawa K, Izawa-Ishizawa Y, Ohnishi S, Motobayashi Y, Kawazoe K, Hamano S, et al. Quercetin glucuronide inhibits cell migration and proliferation by platelet-derived growth factor in vascular smooth muscle cells. J Pharmacol Sci 2009; 109: 257–64.
Wu LF . Study on Tannin fraction from Phyllanthus Emblica L in vivo [dissertation]. Beijing: Beijing University of Chinese Medicine; 2014.
Singh T, Sharma SD, Katiyar SK . Grape proanthocyanidins induce apoptosis by loss of mitochondrial membrane potential of human non-small cell lung cancer cells in vitro and in vivo. PLoS One 2011; 6: e27444.
Kuo PL, Hsu YL, Lin TC, Chang JK, Lin CC . Induction of cell cycle arrest and apoptosis in human non-small cell lung cancer A549 cells by casuarinin from the bark of Terminalia arjuna Linn. Anticancer Drugs 2005; 16: 409–15.
Liu J, Yang Q, Wang MZ, W, G YJ . Matrix metalloproteinases and metastasis of lung cancer. Modern Prevent Med 2003; 30: 689–93.
Polacheck WJ, Zervantonakis IK, Kamm RD . Tumor cell migration in complex microenvironments. Cell Mol Life Sci 2013; 70: 1335–56.
Doddareddy MR, Rawling T, Ammit AJ . Targeting mitogen-activated protein kinase phosphatase-1 (MKP-1): structure-based design of MKP-1 inhibitors and upregulators. Curr Med Chem 2012; 19: 163–73.
Smith WE, Kane AV, Campbell ST, Acheson DW, Cochran BH, Thorpe CM . Shiga toxin 1 triggers a ribotoxic stress response leading to p38 and JNK activation and induction of apoptosis in intestinal epithelial cells. Infect Immun 2003; 71: 1497–504.
Zhan YH, Sun M, Liu J, Liu YP, Qu XJ, Hou KZ, et al. Role of ERK signaling pathway in β-elemene-induced apoptosis in human renal cell carcinoma cells. Chin J Cancer Prev Treat 2012; 19: 321–3.
Zhen YS . Anticancer drug research and developments. 1st ed. Beijing: Chemical Industry Press; 2004.
Wang WX, Chen SX, Wen JF, Xiao GM, Zhou SL . Expression and metastasis prognosis of CD44V6 MMP2, MMP9, TIMP1 and TIMP2 in non-small cell lung cancer. Chin Med Engineer 2007; 15: 122–5.
Lin F, Chengyao X, Qingchang L, Qianze D, Enhua W, Yan W . CRKL promotes lung cancer cell invasion through ERK-MMP9 pathway. Mol Carcinog 2014. doi: 10.1002/mc.22148.
Chen YY, Liu FC, Chou PY, Chien YC, Chang WS, Huang GJ, et al. Ethanol extracts of fruiting bodies of Antrodia cinnamomea suppress CL1-5 human lung adenocarcinoma cells migration by inhibiting matrix metalloproteinase-2/9 through ERK, JNK, p38, and PI3K/Akt signaling pathways. Evid Based Complement Alternat Med 2012; 2012: 378415.
Weiss MB, Abel EV, Mayberry MM, Basile KJ, Berger AC, Aplin AE . TWIST1 is an ERK1/2 effector that promotes invasion and regulates MMP-1 expression in human melanoma cells. Cancer Res 2012; 72: 6382–92.
Tsai HC, Su HL, Huang CY, Fong YC, Hsu CJ, Tang CH . CTGF increases matrix metalloproteinases expression and subsequently promotes tumor metastasis in human osteosarcoma through down-regulating miR-519d. Oncotarget 2014; 5: 3800–12.
Wang JR, Li XH, Gao XJ, An SC, Liu H, Liang J, et al. Expression of MMP-13 is associated with invasion and metastasis of papillary thyroid carcinoma. Eur Rev Med Pharmacol Sci 2013; 17: 427–35.
Acknowledgements
This project was supported by the National Natural Science Foundation of China (81274187 and 81274006).
Author information
Authors and Affiliations
Corresponding authors
Rights and permissions
About this article
Cite this article
Zhao, Hj., Liu, T., Mao, X. et al. Fructus phyllanthi tannin fraction induces apoptosis and inhibits migration and invasion of human lung squamous carcinoma cells in vitro via MAPK/MMP pathways. Acta Pharmacol Sin 36, 758–768 (2015). https://doi.org/10.1038/aps.2014.130
Received:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/aps.2014.130
Keywords
This article is cited by
-
Phase I study of procaspase-activating compound-1 (PAC-1) in the treatment of advanced malignancies
British Journal of Cancer (2023)
-
Mebendazole augments sensitivity to sorafenib by targeting MAPK and BCL-2 signalling in n-nitrosodiethylamine-induced murine hepatocellular carcinoma
Scientific Reports (2019)
-
Viridicatol and viridicatin isolated from a shark-gill-derived fungus Penicilliumpolonicum AP2T1 as MMP-2 and MMP-9 inhibitors in HT1080 cells by MAPKs signaling pathway and docking studies
Medicinal Chemistry Research (2019)
-
The effects of different meditation exercises on sleep quality in older people: a network meta-analysis
European Geriatric Medicine (2019)
-
Fangjiomics: revealing adaptive omics pharmacological mechanisms of the myriad combination therapies to achieve personalized medicine
Acta Pharmacologica Sinica (2015)
