Browse > Article
http://dx.doi.org/10.15188/kjopp.2022.02.36.1.1

The Tuber Extract of Pinellia ternata (Thunb.) Brei Suppresses Cancer Cell Migration by Regulating Tumor-associated Macrophages  

Park, Shin-Hyung (Department of Pathology, College of Korean Medicine, Dong-eui University)
Publication Information
Journal of Physiology & Pathology in Korean Medicine / v.36, no.1, 2022 , pp. 1-6 More about this Journal
Abstract
The tuber of Pinellia ternata (Thunb.) Brei (TPT) used in traditional Oriental medicine for the treatment of cough, sputum, vomiting, and insomnia, possesses antioxidant, antibacterial, and anti-inflammatory effects. Although recent studies have reported the anticancer effects of TPT in several cancer cells, it is still unclear whether TPT regulates tumor-associated macrophage (TAM) characterized by the immunosuppressive M2 macrophage phenotype. Our results showed that the ethanol extract of TPT (ETPT) suppressed the migration of RAW264.7 mouse macrophage cells and THP-1 human monocytes differentiated into macrophages towards the conditioned media (CM) collected from lung cancer cells, suggesting that ETPT would attenuate the recruitment of macrophages into tumors. In addition, ETPT suppressed the interleukin (IL)-4 or IL-6-induced M2 macrophage polarization in RAW264.7 cells. ETPT treatment not only downregulated the mRNA expression of M2 macrophage markers including arginase-1, mannose receptor C type 1 (MRC-1), and IL-10, but also inhibited the phosphorylation of signal transducer and activator of transcription 3 (STAT3) and STAT6, general regulators of M2 macrophage polarization. Finally, the transwell assay results showed that the CM from M2-polarized RAW264.7 cells increased the migration of mouse lewis lung carcinoma (LLC) cells, while those from RAW264.7 cells co-treated with ETPT and IL-6 significantly reduced the migration of LLC cells. Taken together, our observations clearly demonstrate that ETPT suppressed the cancer cell migration by regulating macrophage recruitment and M2 macrophage polarization.
Keywords
Tuber of Pinellia ternata (Thunb.) Brei; Tumor-associated macrophage; M2 macrophage; Cancer cell migration;
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
연도 인용수 순위
1 Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature. 2008;454(7203):436-44.   DOI
2 Almatroodi SA, McDonald CF, Darby IA, Pouniotis DS. Characterization of M1/M2 tumour-associated macrophages (TAMs) and Th1/Th2 cytokine profiles in patients with NSCLC. Cancer Microenviron. 2016;9(1):1-11.   DOI
3 DeNardo DG, Ruffell B. Macrophages as regulators of tumour immunity and immunotherapy. Nat Rev Immunol. 2019;19(6):369-82.   DOI
4 Pan Y, Yu Y, Wang X, Zhang T. Tumor-Associated Macrophages in Tumor Immunity. Front Immunol. 2020;11:583084.   DOI
5 Roszer T. Understanding the Mysterious M2 Macrophage through Activation Markers and Effector Mechanisms. Mediators Inflamm. 2015;2015:816460.   DOI
6 The Jointly Published Textbook Compilation Committee of Oriental College of Medicine Nationwide Department. Herbology. Seoul: Younglim press; 2004.
7 Tang D, Yan R, Sun Y, Kai G, Chen K, Li J. Material basis, effect, and mechanism of ethanol extract of Pinellia ternata tubers on oxidative stress-induced cell senescence. Phytomedicine. 2020;77:153275.   DOI
8 Lee JY, Park NH, Lee W, Kim EH, Jin YH, Seo EK, Hong J. Comprehensive chemical profiling of Pinellia species tuber and processed Pinellia tuber by gas chromatography-massspectrometry and liquid chromatography atmospheric pressure chemical ionization-tandem mass spectrometry. J Chromatogr A. 2016;1471:164-77.   DOI
9 Li Y, Li D, Chen J, Wang S. A polysaccharide from Pinellia ternata inhibits cell proliferation and metastasis in human cholangiocarcinoma cells by targeting of Cdc42 and 67kDa Laminin Receptor (LR). Int J Biol Macromol. 2016;93(Pt A):520-5.   DOI
10 Zhou W, Gao Y, Xu S, Yang Z, Xu T. Purification of a mannose-binding lectin Pinellia ternata agglutinin and its induction of apoptosis in Bel-7404 cells. Protein Expr Purif. 2014;93:11-7.   DOI
11 Fu XL, Duan W, Su CY, Mao FY, Lv YP, Teng YS, et al. Interleukin 6 induces M2 macrophage differentiation by STAT3 activation that correlates with gastric cancer progression. Cancer Immunology, Immunotherapy. 2017;66(12):1597-1608.   DOI
12 Mauer J, Chaurasia B, Goldau J, Vogt MC, Ruud J, Nguyet KD, et al. Signaling by IL-6 promotes alternative activation of macrophages to limit endotoxemia and obesity-associated resistance to insulin. Nature Immunology. 2014;15(5):423-30.   DOI
13 Park HJ, Chi GY, Choi YH, Park SH. The root bark of Morus alba L. regulates tumor-associated macrophages by blocking recruitment and M2 polarization of macrophages. Phytother Res. 2020;34(12):3333-44.   DOI
14 Bernsmeier C, van der Merwe S, Perianin A. The innate immune cells in cirrhosis. J Hepatol. 2020;73(1):186-201.   DOI
15 Liu YF, Zhuang KH, Chen B, Li PW, Zhou X, Jiang H, Zhong LM, Liu FB. Expansion and activation of monocytic-myeloid-derived suppressor cell via STAT3/arginase-I signaling in patients with ankylosing spondylitis. Arthritis Res Ther. 2018;20(1):168.   DOI
16 Vasquez-Dunddel D, Pan F, Zeng Q, Gorbounov M, Albesiano E, Fu J, et al. STAT3 regulates arginase-I in myeloid-derived suppressor cells from cancer patients. J Clin Invest. 2013;123(4):1580-9.   DOI
17 Hutchins AP, Diez D, Miranda-Saavedra D. The IL-10/STAT3-mediated anti-inflammatory response: recent developments and future challenges. Brief Funct Genomics. 2013;12(6):489-98.   DOI
18 LI X, Zhao A, Yang J, Qian J, Chen L. Study on Role of Mucin 5AC in Malignant Tumors Based on Theory of "Body Fluid" and "Phlegm and Retained Fluid". Liaoning J Trad Chin Med. 2020;8:51-4.
19 Zhu C, Kros JM, Cheng C, Mustafa D. The contribution of tumor-associated macrophages in glioma neo-angiogenesis and implications for antiangiogenic strategies. Neurooncology. 2017;19(11):1435-46.
20 Ngambenjawong C, Gustafson HH, Pun SH. Progress in tumor-associated macrophage (TAM)-targeted therapeutics. Adv Drug Deliv Rev. 2017;114:206-21.   DOI
21 Kwon GR, Moon IS, Lee WC. Neuroprotective Effects of Pinelliae Rhizoma Water-Extract by Suppression of Reactive Oxygen Species and Mitochondrial Membrane Potential Loss in a Hypoxic Model of Cultured Rat Cortical Cells. Journal of Life Science. 2009;19(5):598-606.   DOI
22 Hanahan D, Coussens LM. Accessories to the crime: Functions of cells recruited to the tumor microenvironment. Cancer Cell. 2012;21(3):309-22.   DOI
23 Hu M, Liu Y, Wang L, Wang J, Li L, Wu C. Purification, Characterization of Two Polysaccharides from Pinelliae Rhizoma Praeparatum Cum Alumine and Their Anti-Inflammatory Effects on Mucus Secretion of Airway Epithelium. Int J Mol Sci. 2019;20(14):3553.   DOI
24 Jiang H, Harris MB, Rothman P. IL-4/IL-13 signaling beyond JAK/STAT, J Allergy Clin Immunol. 2000;105:1063e1070.
25 Yin Z, Ma T, Lin Y, Lu X, Zhang C, Chen S, Jian Z. IL-6/STAT3 pathway intermediates M1/M2 macrophage polarization during the development of hepatocellular carcinoma. J Cell Biochem. 2018;119(11):9419-32.   DOI
26 Lee SJ, Evers S, Roeder D, Parlow AF, Risteli J, Risteli L, et al. Mannose receptor-mediated regulation of serumglycoprotein homeostasis. Science. 2002;295(5561): 1898-901.   DOI