Browse > Article
http://dx.doi.org/10.3831/KPI.2019.22.036

Naesohwangryeon-tang Induced Apoptosis and Autophagy in A549 Human Lung Cancer Cells  

Kim, Hong Jae (Anti-Aging Research Center, Dong-eui University)
Jeong, Jin-Woo (Freshwater Bioresources Utilization Bureau, Nakdonggang National Institute of Biological Resoureces)
Park, Cheol (Department of Molecular Biology, College of Natural Sciences and Human Ecology, Dong-eui University)
Choi, Yung Hyun (Anti-Aging Research Center, Dong-eui University)
Hong, Su Hyun (Anti-Aging Research Center, Dong-eui University)
Publication Information
Journal of Pharmacopuncture / v.22, no.4, 2019 , pp. 269-278 More about this Journal
Abstract
Objectives: Naesohwangryeon-tang (NHT) is a type of traditional herbal formula, however, little is known about its antitumor activity. In this study, the antitumor properties of NHT was evaluated in human lung adenocarcinoma cells. Methods: To check the inhibitory effect of NHT, MTT assay was performed. Cell cycle analysis and detection of ROS production were conducted by flow cytometry. To evaluate the signaling pathway, Western blotting was conducted. Results: Our results showed that the decrease of cell proliferation by NHT stimulation occurred more significantly in A549 cells than in NCI-H460 cells. In addition, NHT-induced apoptosis was associated with the activation of caspases and production of reactive oxygen species (ROS). NHT-induced apoptosis was attenuated after pretreatments with z-VAD-fmk or N-acetylcysteine, suggesting that NHT-induced apoptosis was caspaseand ROS-dependent. Interestingly, NHT treatment led to the development of autophagic vesicular organelles and upregulation of several autophagy-related genes. The pretreatment of bafilomycin A1 decreased apoptosis slightly but increased cell viability in the presence of NHT. Conclusion: These findings indicated that NHT induces both apoptosis and cell-protective autophagy in human lung cancer cells. This data suggests that NHT might be a novel herbal drug for lung cancer.
Keywords
A549 Lung Cancer Cells; Apoptosis; Autophagy; Caspases; Naesohwangryeon-tang; Reactive Oxygen Species;
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
연도 인용수 순위
1 Siegel R, Naishadham D, Jemal A. Cancer statistics. CA Cancer J Clin. 2012;62(1):10-29.   DOI
2 Cho KM, Keam B, Kim TM, Lee SH, Kim DW, Heo DS. Clinical efficacy of erlotinib, a salvage treatment for non-small cell lung cancer patients following gefitinib failure. Korean J Intern Med. 2015;30(6):891-8.   DOI
3 Wu T, Wang MC, Jing L, Liu ZY, Guo H, Liu Y, et al. Autophagy facilitates lung adenocarcinoma resistance to cisplatin treatment by activation of AMPK/mTOR signaling pathway.Drug Des Devel Ther 2015;9:6421-31.
4 Kapp FG, Sommer A, Kiefer T, Dolken G, Haendler B. 5-alpha-reductase type I (SRD5A1) is up-regulated in non-small cell lung cancer but does not impact proliferation, cell cycle distribution or apoptosis. Cancer Cell Int. 2012;12(1):1.   DOI
5 Pyo JO, Nah J, Jung YK. Molecules and their functions in autophagy. Exp Mol Med. 2012;44(2):73-80   DOI
6 Mizushima N, Yoshimorim T, Levine B. Methods in mammalian autophagy research. Cell. 2010;140(3):313-26.   DOI
7 Choi KS. Autophagy and cancer. Exp Mol Med. 2012;44(2):109-20.   DOI
8 Levine B, Kroemer G. Autophagy in the pathogenesis of disease. Cell. 2008;132(1):27-42.   DOI
9 Khan M, Maryam A, Zhang H, Mehmood T, Ma T. Killing cancer with platycodin D through multiple mechanisms. J Cell Mol Med 2016;20(3):389-402.   DOI
10 Hsiao WL, Liu L. The role of traditional Chinese herbal medicines in cancer therapy-from TCM theory to mechanistic insights. Planta Med. 2010;76(11):1118-31.   DOI
11 An BJ, Lee CE, Son JH, Lee JY, Park TS, Park JM, er al. Antioxidant, Anticancer and antibacterial Activities of Naesohwangryntang and its Ingredients, Kor J Herbology. 2005;20(4):17-26.
12 Yi CH, Yuan J. The Jekyll and Hyde functions of caspases. Dev Cell. 2009;16(1):21-34.   DOI
13 Nunez G, Benedict MA, Hu Y, Inohara N. Caspases: the proteases of the apoptotic pathway. Oncogene. 1998;17(25):3237-45.   DOI
14 Na PY, Chye SM, Ng ChH, Koh RY, Tiong YL, Pui LP, et al. Clinacanthus Nutans Hexane Extracts Induce Apoptosis Through a Caspase-Dependent Pathway in Human Cancer Cell Lines. Asian Pac J Cancer Prev. 2017;18(4):917-26.
15 Choi EO, Park C, Hwang HJ, Hong SH, Kim GY, Cho EJ, et al. Baicalein induces apoptosis via ROS-dependent activation of caspases in human bladder cancer 5637 cells. Int J Oncol. 2016;49(3):1009-18.   DOI
16 Hua P, Sun M, Zhang G, Zhang Y, Tian X, Li X, et al. Cepharanthine induces apoptosis through reactive oxygen species and mitochondrial dysfunction in human non-small-cell lung cancer cells. Biochem Biophys Res Commun. 2015;460(2):136-42.   DOI
17 Macek C. East meets West to balance immunologic yin and yang. JAMA. 1984;251(4):433-5, 439.   DOI
18 Shalini S, Dorstyn L, Dawar S, Kumar S. Old, new and emerging functions of caspases. Cell Death Differ. 2015;22(4):526-39.   DOI
19 Graf RP, Keller N, Barbero S, Stupack D. Caspase-8 as a regulator of tumor cell motility. Curr Mol Med. 2014;14(2):246-54.   DOI
20 Park C, Cha HJ, Choi EO, Lee H, Hwang-Bo H, Ji SY et al., Isorhamnetin Induces Cell Cycle Arrest and Apoptosis Via Reactive Oxygen Species-Mediated AMP-Activated Protein Kinase Signaling Pathway Activation in Human Bladder Cancer Cells. Cancers (Basel). 2019;11(10),1494.   DOI
21 Vijayan V, Verstreken P. Autophagy in the presynaptic compartment in health and disease. J Cell Biol 2017;216(7):1895-1906.   DOI
22 Lorin S, Hamai A, Mehrpour M, Codogno P. Autophagy regulation and its role in cancer. Semin Cancer Biol. 2013;23(5):361-79.   DOI
23 Hooper KM, Barlow PG, Stevens C, Henderson P. Inflammatory Bowel Disease Drugs: A Focus on Autophagy. J Crohns Colitis. 2017;11(1):118-127.   DOI
24 Kimmelman AC. The dynamic nature of autophagy in cancer. Genes Dev. 2011;25(19):1999-2010.   DOI
25 Lin SR, Fu YS, Tsai MJ, Cheng H, Weng CF. Natural Compounds from Herbs that can Potentially Execute as Autophagy Inducers for Cancer Therapy. Int J Mol Sci. 2017;18(7):1412.   DOI
26 Rosenfeldt MT, Ryan KM. The role of autophagy in tumour development and cancer therapy. Expert Rev Mol Med. 2009;11:e36.   DOI
27 Wang Y, Zhang J, Huang ZH, Huang XH, Zheng WB, Yin XF, et al. Isodeoxyelephantopin induces protective autophagy in lung cancer cells via Nrf2-p62-keap1 feedback loop. Cell Death Dis. 2017;8(6):e2876.   DOI
28 Yu L, Shang ZF, Hsu FM, Zhang Z, Tumati V, Lin YF, et al. NSCLC cells demonstrate differential mode of cell death in response to the combined treatment of radiation and a DNA-PKCs inhibitor. Oncotarget. 2015;6(6):3848-60.   DOI
29 Saleh T, Cuttino L, Gewirtz DA. Autophagy is not uniformly cytoprotective: a personalized medicine approach for autophagy inhibition as a therapeutic strategy in non-small cell lung cancer. Biochim Biophys Acta. 2016;1860(10):2130-6.   DOI
30 Chung SJ, Nagaraju GP, Nagalingam A, Muniraj N, Kuppusamy P, Walker A, et al. ADIPOQ/adiponectin induces cytotoxic autophagy in breast cancer cells through STK11/LKB1-mediated activation of the AMPK-ULK1 axis. Autophagy. 2017;13(8):1386-1403.   DOI
31 Fulda S. Autophagy in Cancer Therapy. Front Oncol. 2017;7:128.   DOI