Naesohwangryeon-tang Induced Apoptosis and Autophagy in A549 Human Lung Cancer Cells
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
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.
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.
참고문헌 (31)
- Siegel R, "Cancer statistics", CA Cancer J Clin, 62(1), pp.10~29 (2012)
- 조경민, "Clinical efficacy of erlotinib, a salvage treatment for non-small cell lung cancer patients following gefitinib failure", The Korean Journal of Internal Medicine, 30(6), pp.891~898 (2015), 대한내과학회[DOI]
- Wu T, "Autophagy facilitates lung adenocarcinoma resistance to cisplatin treatment by activation of AMPK", mTOR signaling pathway, 2015, pp.9, 6421~6431
- Kapp FG, "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, 12(1), pp.1~ (2012)
- 표종옥, "Molecules and their functions in autophagy", Experimental and Molecular Medicine, 44(2), pp.73~80 (2012), 생화학분자생물학회
- Mizushima N, "Methods in mammalian autophagy research", Cell, 140(3), pp.313~326 (2010)
- 최경숙, "Autophagy and cancer", Experimental and Molecular Medicine, 44(2), pp.109~120 (2012), 생화학분자생물학회
- Levine B, "Autophagy in the pathogenesis of disease", Cell, 132(1), pp.27~42 (2008)
- Khan M, "Killing cancer with platycodin D through multiple mechanisms", J Cell Mol Med, 20(3), pp.389~402 (2016)
- Hsiao WL, "The role of traditional Chinese herbal medicines in cancer therapy-from TCM theory to mechanistic insights", Planta Med, 76(11), pp.1118~1131 (2010)
- 안봉전, "내소황련탕(內疎黃連湯) 및 구성약재의 항산화효과 검증과 항암 및 항균효과", 대한본초학회지, 20(4), pp.17~26 (2005), 대한본초학회
- Yi CH, "The Jekyll and Hyde functions of caspases", Dev Cell, 16(1), pp.21~34 (2009)
- Nuñez G, "Caspases : the proteases of the apoptotic pathway", Oncogene, 17(25), pp.3237~3245 (1998)
- Na PY, "Clinacanthus Nutans Hexane Extracts Induce Apoptosis Through a Caspase-Dependent Pathway in Human Cancer Cell Lines", Asian Pac J Cancer Prev, 18(4), pp.917~926 (2017)
- Choi EO, "Baicalein induces apoptosis via ROS-dependent activation of caspases in human bladder cancer 5637 cells", Int J Oncol, 49(3), pp.1009~1018 (2016)
- Hua P, "Cepharanthine induces apoptosis through reactive oxygen species and mitochondrial dysfunction in human non-small-cell lung cancer cells", Biochem Biophys Res Commun, 460(2), pp.136~142 (2015)
- Macek C, "East meets West to balance immunologic yin and yang", JAMA, 251(4), pp.433~435 (1984)
- Shalini S, "Old, new and emerging functions of caspases", Cell Death Differ, 22(4), pp.526~539 (2015)
- Graf RP, "Caspase-8 as a regulator of tumor cell motility", Curr Mol Med, 14(2), pp.246~254 (2014)
- Park C, "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), 11(10), pp.1494~ (2019)
- Vijayan V, "Autophagy in the presynaptic compartment in health and disease", J Cell Biol, 216(7), pp.1895~1906 (2017)
- Hooper KM, "Inflammatory Bowel Disease Drugs : A Focus on Autophagy", J Crohns Colitis, 11(1), pp.118~127 (2017)
- Kimmelman AC, "The dynamic nature of autophagy in cancer", Genes Dev, 25(19), pp.1999~2010 (2011)
- Lin SR, "Natural Compounds from Herbs that can Potentially Execute as Autophagy Inducers for Cancer Therapy", Int J Mol Sci, 18(7), pp.1412~ (2017)
- Lorin S, "Autophagy regulation and its role in cancer", Semin Cancer Biol, 23(5), pp.361~379 (2013)
- Rosenfeldt MT, "The role of autophagy in tumour development and cancer therapy", Expert Rev Mol Med, 11, pp.e36~ (2009)
- Wang Y, "Isodeoxyelephantopin induces protective autophagy in lung cancer cells via Nrf2-p62-keap1 feedback loop", Cell Death Dis, 8(6), pp.e2876~ (2017)
- Yu L, "NSCLC cells demonstrate differential mode of cell death in response to the combined treatment of radiation and a DNA-PKCs inhibitor", Oncotarget, 6(6), pp.3848~3860 (2015)
- Saleh T, "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, 1860(10), pp.2130~2136 (2016)
- Chung SJ, "ADIPOQ", adiponectin induces cytotoxic autophagy in breast cancer cells through STK11, Autophagy, pp.2017, 13(8)[DOI]
- Fulda S, "Autophagy in Cancer Therapy", Front Oncol, 7, pp.128~ (2017)