Browse > Article
http://dx.doi.org/10.14374/HFS.2020.28.1.15

Comparison of Anti-cancer Potentials of Water Extracts of Bigihwan, Daechilgithang and Mokwhyangbinranghwan in Human Hepatocellular Carcinoma Cells  

Kim, Min Yeong (Anti-Aging Research Center, Dong-eui University)
Lee, Hyesook (Anti-Aging Research Center, Dong-eui University)
Hong, Su Hyun (Anti-Aging Research Center, Dong-eui University)
Park, Cheol (Department of Molecular Biology, College of Natural Sciences, Dong-eui University)
Choi, Yung Hyun (Anti-Aging Research Center, Dong-eui University)
Publication Information
Herbal Formula Science / v.28, no.1, 2020 , pp. 15-27 More about this Journal
Abstract
Objectives : We selected three herb-combined remedies, Bigihwan (BGH), Daechilgitang (DCGT) and Mokwhyangbinranghwan (MHBRH), through Donguibogam text-mining analysis, and evaluated their anti-cancer effects on human hepatocellular carcinoma Hep3B cells. Methods : Cytotoxicity was assessed by an MTT assay. Apoptosis rate, autophagy and ROS level were detected by flow cytometry. The autophagy was also observed by Cyto-ID staining fluorescence microscopy. The expression of autophagy, mitophagy and pexophagy regulatory proteins was detected by Western blot analysis. Results : BGH showed the strongest effect among the three prescriptions in inhibiting Hep3B cell viability, which was associated with the induction of apoptosis and autophagy. Autophagy blockers improved cell viability and reduced apoptosis after BGH and DCGT treatments, indicating that autophagy by these prescriptions enhanced Hep3B cells against their cytotoxicity. However, MHBRH enhanced the reduction of cell viability and apoptosis by autophagy blockers. Induction of autophagy by BGH treatment was associated with mitophagy due to mitochondrial dysfunction than DCGT and MHBRH-treated cells. In addition, induction of apoptosis by BGH treatment was ROS-dependent and showed the possibility of pexophagy involvement. Conclusion : Although further studies need to be conducted to study the efficacy and mechanism of accurate anticancer activity, the present results will serve as important sources of understanding the mechanism of action of herbal remedies prescribed for liver disease as documented in Donguibogam.
Keywords
Bigihwan; Daechilgitang; Mokwhyangbinranghwan; liver cancer; apoptosis; autophagy; ROS;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Waterham HR, Ferdinandusse S, Wanders RJ. Human disorders of peroxisome metabolism and biogenesis. Biochim Biophys Acta. 2016;1863:922-33.   DOI
2 Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69:7-34.   DOI
3 Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65:87-108.   DOI
4 Brown ZJ, Heinrich B, Greten TF. Mouse models of hepatocellular carcinoma: an overview and highlights for immunotherapy research. Nat Rev Gastroenterol Hepatol. 2018;15:536-54.   DOI
5 Soussi T, Ishioka C, Claustres M, Beroud C. Locus-specific mutation databases: pitfalls and good practice based on the p53 experience. Nat Rev Cancer. 2006;6:83-90.   DOI
6 Xu W, Yu J, Wong VW. Mechanism and prediction of HCC development in HBV infection. Best Pract Res Clin Gastroenterol. 2017;31:291-8.   DOI
7 Chow HC, So TH, Choi HCW, Lam KO. Literature review of traditional Chinese medicine herbs-induced liver injury from an oncological perspective with RUCAM. Integr Cancer Ther. 2019;18:1534735419869479.
8 Xi SY, Minuk GY. Role of traditional Chinese medicine in the management of patients with hepatocellular carcinoma. World J Hepatol. 2018;10:799-806.   DOI
9 Heo J, 2012. In: Kang C.H. (Eds.), DonguiBogam (Principles and Practice of Eastern Medicine). Seoul, Korea, Bubin Publishers Co.
10 Mattiuzzi C, Lippi G. Current cancer epidemiology. J Epidemiol Glob Health. 2019;9:217-22.   DOI
11 Han SI, Kang BK. Antitumor effects of bigihwan on tumor cells derived from leukemia and lymphoma patients. J Int Korean Med. 1991;12:1-15.
12 Kang DG, Kang BK. Antitumor effects of sigbunhwan and bigihwan on tumor cells derived from leukemia and lymphoma patients. J Int Korean Med. 1991;12:96-112.
13 Kim HY, Ko SJ, Bang CH, Shin SH, Lee DY, Lee I. Effects of daechilgi-tang on glutamate-induced apoptosis in C6 glial cells. Korean J Orient Int Med. 2010;31:693-705.
14 Lin L, Baehrecke EH. Autophagy, cell death, and cancer. Mol Cell Oncol. 2015;2:e985913.   DOI
15 Baik TH, Lee I. An experimental study on the effects of mkwhyangbinrang-whan. J Int Korean Med. 1997;18:373-90.
16 Wang Y, Zhong J, Bai J, Tong R, An F, Jiao P, He L, Zeng D, Long E, Yan J, Yu J, Cai L. The application of natural products in cancer therapy by targeting apoptosis pathways. Curr Drug Metab. 2018;19:739-49.   DOI
17 D'Arcy MS. Cell death: a review of the major forms of apoptosis, necrosis and autophagy. Cell Biol Int. 2019;43:582-92.   DOI
18 Lee YS, Lee DH, Choudry HA, Bartlett DL, Lee YJ. Ferroptosis-induced endoplasmic reticulum stress: Cross-talk between ferroptosis and apoptosis. Mol Cancer Res. 2018;16:1073-6.   DOI
19 Yan X, Zhou R, Ma Z. Autophagy-cell survival and death. Adv Exp Med Biol. 2019;1206:667-96.   DOI
20 Condello M, Pellegrini E, Caraglia M, Meschini S. Targeting autophagy to overcome human diseases. Int J Mol Sci. 2019;20:E725.   DOI
21 Russo M, Russo GL. Autophagy inducers in cancer. Biochem Pharmacol. 2018;153:51-61.   DOI
22 Wesselborg S, Stork B. Autophagy signal transduction by ATG proteins: from hierarchies to networks. Cell Mol Life Sci. 2015;72:4721-57.   DOI
23 Galluzzi L, Green DR. Autophagy-independent functions of the autophagy machinery. Cell. 2019;177:1682-99.   DOI
24 Castino R, Bellio N, Follo C, Murphy D, Isidoro C. Inhibition of PI3k class III-dependent autophagy prevents apoptosis and necrosis by oxidative stress in dopaminergic neuroblastoma cells. Toxicol Sci. 2010;117:152-62.   DOI
25 Wanders RJ, Waterham HR, Ferdinandusse S. Metabolic interplay between peroxisomes and other subcellular organelles including mitochondria and the endoplasmic reticulum. Front Cell Dev Biol. 2016;3:83.
26 Yamamoto A, Tagawa Y, Yoshimori T, Moriyama Y, Masaki R, Tashiro Y. Bafilomycin A1 prevents maturation of autophagic vacuoles by inhibiting fusion between autophagosomes and lysosomes in rat hepatoma cell line, H-4-II-E cells. Cell Struct Funct. 1998; 23:33-42.   DOI
27 Biel TG, Rao VA. Mitochondrial dysfunction activates lysosomal-dependent mitophagy selectively in cancer cells. Oncotarget. 2017;9:995-1011.   DOI
28 Kim I, Rodriguez-Enriquez S, Lemasters JJ. Selective degradation of mitochondria by mitophagy. Arch Biochem Biophys. 2007;462:245-53.   DOI
29 Miller S, Muqit MMK. Therapeutic approaches to enhance PINK1/Parkin mediated mitophagy for the treatment of Parkinson's disease. Neurosci Lett. 2019;705:7-13.   DOI
30 Youle RJ, Narendra DP. Mechanisms of mitophagy. Nat Rev Mol Cell Biol. 2011;12:9-14.   DOI
31 Poirier Y, Antonenkov VD, Glumoff T, Hiltunen JK. Peroxisomal beta-oxidation-a metabolic pathway with multiple functions. Biochim Biophys Acta. 2006;1763:1413-26.   DOI
32 Du H, Kim S, Hur YS, Lee MS, Lee SH, Cheon CI. A cytosolic thioredoxin acts as a molecular chaperone for peroxisome matrix proteins as well as antioxidant in peroxisome. Mol Cells 2015;38:187-94.   DOI
33 Fransen M, Nordgren M, Wang B, Apanasets O. Role of peroxisomes in ROS/RNS-metabolism: implications for human disease. Biochim Biophys Acta. 2012;1822:1363-73.   DOI
34 Honsho M, Yamashita S, Fujiki Y. Peroxisome homeostasis: Mechanisms of division and selective degradation of peroxisomes in mammals. Biochim Biophys Acta. 2016;1863:984-91.   DOI
35 Bolhassani A. Cancer chemoprevention by natural carotenoids as an efficient strategy. Anticancer Agents Med Chem. 2015;15:1026-231.   DOI
36 Giannopoulou EA, Emmanouilidis L, Sattler M, Dodt G, Wilmanns M. Towards the molecular mechanism of the integration of peroxisomal membrane proteins. Biochim Biophys Acta. 2016;1863:863-9.   DOI
37 Kiel JA, Veenhuis M, van der Klei IJ. PEX genes in fungal genomes: common, rare or redundant. Traffic. 2006;7:1291-303.   DOI
38 Platta HW, Hagen S, Reidick C, Erdmann R. The peroxisomal receptor dislocation pathway: to the exportomer and beyond. Biochimie. 2014;98:16-28.   DOI
39 Badrinath N. Yoo SY. Mitochondria in cancer: In the aspects of tumorigenesis and targeted therapy. Carcinogenesis. 2018;39:1419-30.   DOI
40 Moloney JN, Cotter TG. ROS signalling in the biology of cancer. Semin Cell Dev Biol 2018;80:50-64.   DOI
41 Galadari S, Rahman A, Pallichankandy S, Thayyullathil F. Reactive oxygen species and cancer paradox: To promote or to suppress? Free Radic Biol Med. 2017:104:144-64.   DOI
42 Fulda S, Debatin KM. Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy. Oncogene. 2006;25:4798-811.   DOI
43 Hata AN, Engelman JA, Faber AC. The BCL2 family: Key mediators of the apoptotic response to targeted anticancer therapeutics. Cancer Discov. 2015;5:475-87.   DOI