Browse > Article

Anti-cancer Effects of Palbohoichoon-tang on Neuroblastoma Cells  

An, Jung-Hwan (YacCheon Oriental Medical Clinic)
Cho, Mun-Young (Dept. of Internal Medicine, College of Oriental Medicine, Won-Kwang University)
Woo, Chan (Dept. of Internal Medicine, College of Oriental Medicine, Won-Kwang University)
Shin, Yong-Jin (Dept. of Internal Medicine, College of Oriental Medicine, Won-Kwang University)
Shin, Sun-Ho (Dept. of Internal Medicine, College of Oriental Medicine, Won-Kwang University)
Publication Information
The Journal of Internal Korean Medicine / v.35, no.1, 2014 , pp. 79-91 More about this Journal
Abstract
Objectives : To investigate the anti-cancer effect of Palbohoichoon-tang (PBHCT) extracts. Methods : The cell viability was assessed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MMT) assay and cell morphological changes were microscopically analyzed after staining with $10{\mu}M$ 2-[4-amidinophenyl]-6-indolecarbamidine dihydrochloride (DAPI) and TUNEL. We also analyzed expression of Bcl2, $Bcl_{xL}$, Bax, procaspase-3, procaspase-9, and procyclic acidic repetitive protein (PARP) by western blot method. Results : Observations showed that PBHCT induced the apoptotic cell death proved by increased sub-G1 phase cell population, apoptotic body formation and chromatin condensation. Western blot analysis of total cell lysates revealed that the PBHCT induced cleavage of caspase-9, caspase-3 and poly (ADP-ribose) polymerase (PARP). In addition, PBHCT dose-dependently increased the activity of caspase-9, caspase-3 and PARP-1. Furthermore, PBHCT reduced anti-apoptotic Bcl2, $Bcl_{xL}$ expression which contributed to the loss of mitochondrial membrane potential and the activations of caspase-9 and caspase-3. Conclusions : These findings suggest that PBHCT exerts anti-cancer effects on human neuroblastoma SH-SY5Y cells by inducing apoptotic death via down-regulation of anti-apoptotic proteins such as Bcl2 and $Bcl_{xL}$, up-regulation of pro-apoptotic proteins such as Bax, and activation of caspase cascades and PARP-1.
Keywords
SH-SY5Y cell; Anti-cancer effect; Palbohoichoon-tang (PBHCT);
Citations & Related Records
연도 인용수 순위
  • Reference
1 이종대. 새로보는 方藥合編. 서울: 청홍(지상사); 2012, p. 80-5.
2 한국 통계청 사회통계국 인구동향과. 2010년 사망원인통계결과. 대전: 통계청; 2011.
3 주요 질환별 신약개발 동향. 생명공학정책연구센터. 2007.
4 문구, 정병학, 김병주. 암 동서의 결합치료 1. 익산: 원광대학교출판국; 1999, p. 93-8, 258-82, 385-460.
5 황도연. 新增 方藥合編. 서울: 永林社; 2002, p. 123-4.
6 최승훈, 오민석, 송태원, 남기열. 十全大補湯의 免疫增强 및 抗癌 효과. 대전대학교 한의학연구소 논문집 2002;11(1):257-83.
7 Caroppi P, Sinibaldi F, Fiorucci L, Santucci R. Apoptosis and human diseases: mitochondrion damage and lethal role of released cytochrome C as proapoptotic protein. Curr Med Chem 2009; 16(31):4058-65.   DOI   ScienceOn
8 Willimott S, Wagner SD. Post-transcriptional and post-translational regulation of Bcl2. Biochem Soc Trans 2010;38(6):1571-5.   DOI   ScienceOn
9 Barillé-Nion S, Bah N, Véquaud E, Juin P. Regulation of Cancer Cell Survival by BCL2 Family Members upon Prolonged Mitotic Arrest: Opportunities for Anticancer Therapy. Anticancer Res 2012;32(10):4225-33.
10 Boumela I, Assou S, Aouacheria A, Haouzi D, Dechaud H, De Vos J. Involvement of BCL2 family members in the regulation of human oocyte and early embryo survival and death: gene expression and beyond. Reproduction 2011;141(5): 549-61.   DOI   ScienceOn
11 Kelly PN, Strasser A. The role of Bcl-2 and its pro-survival relatives in tumourigenesis and cancer therapy. Cell Death Differ 2011;18(9): 1414-24.   DOI   ScienceOn
12 Schwartz LM, Osborne BA. Ced-3/ICE: evolutionarily conserved regulation of cell death. Bioessays 1994;16(6):387-9.   DOI   ScienceOn
13 Webster KA. Mitochondrial membrane permeabilization and cell death during myocardial infarction: roles of calcium and reactive oxygen species. Future Cardiol 2012;8(6):863-84.   DOI
14 Bauer MK, Wesselborg S, Schulze-Osthoff K. The Caenorhabditis elegans death protein Ced-4 contains a motif with similarity to the mammalian 'death effector domain'. FEBS Lett 1997;402(2-3):256-8.   DOI   ScienceOn
15 Conradt B, Horvitz HR. The C. elegans protein EGL-1 is required for programmed cell death and interacts with the Bcl-2-like protein CED-9. Cell 1998;93(4):519-29.   DOI   ScienceOn
16 MacKenzie SH, Clark AC. Death by caspase dimerization. Adv Exp Med Biol 2012;747:55-73.   DOI
17 Monian P, Jiang X. Clearing the final hurdles to mitochondrial apoptosis: regulation post cytochrome C release. Exp Oncol 2012;34(3): 185-91.
18 Solá S, Morgado AL, Rodrigues CM. Death receptors and mitochondria: Two prime triggers of neural apoptosis and differentiation. Biochim Biophys Acta 2013;1830(1):2160-6.   DOI   ScienceOn
19 Murray P, D Edgar. Regulation of programmed cell death by basement membranes in embryonic development. J Cell Biol 2000;150(5):1215-21.   DOI   ScienceOn
20 Pabla N, Dong Z. Curtailing side effects in chemotherapy: a tale of $PKC\delta$ in cisplatin treatment. Oncotarget 2012;3(1):107-11.
21 허준. 東醫寶鑑. 하동: 동의보감출판사; 2005, p. 1012-3.
22 Bozkurt E, Atmaca H, Kisim A, Uzunoglu S, Uslu R, Karaca B. Effects of Thymus serpyllum Extract on Cell Proliferation, Apoptosis and Epigenetic Events in Human Breast Cancer Cells. Nutr Cancer 2012;64(8):1245-50.   DOI   ScienceOn
23 Meier P, A Finch, and G Evan. Apoptosis in development. Nature 2000;407(6805):796-801.   DOI   ScienceOn
24 Vucic D, Dixit VM, Wertz IE. Ubiquitylation in apoptosis: a post-translational modification at the edge of life and death. Nat Rev Mol Cell Biol 2011;12(7):439-52.   DOI   ScienceOn
25 Franke TF, Kaplan DR, Cantley L. PI3K: downstream AKTion blocks apoptosis. Cell 1997; 88:435-7.   DOI   ScienceOn
26 황규동. 十全大補湯 瓦松 및 十全大補湯加瓦松의 抗癌效果와 免疫反應에 關한 硏究. 대한암한의학회지 1996;2:1-23.
27 황충연. 十全大補湯加味 鹿茸이 마우스의 免疫 反應에 미치는 影響. 원광대학교 대학원. 1989.
28 Fiandalo MV, Kyprianou N. Caspase control: protagonists of cancer cell apoptosis. Exp Oncol 2012;34(3):165-75.
29 Gross A, McDonnell JM, Kormeyer SJ. Bcl-2 family members and the mitochondria in apoptosis. Genes Dev 2000;13:1899-911.
30 Lovat PE, Corazzari M, Goranov B, Piacentini M, Redfern CP. Molecular mechanisms of fenretinide-induced apoptosis of neuroblastoma cells. Ann N Y Acad Sci 2004;1028:81-9.   DOI   ScienceOn
31 Stegh AH, DePinho RA. Beyond effector caspase inhibition: Bcl2L12 neutralizes p53 signaling in glioblastoma. Cell Cycle 2011;10(1):33-8.   DOI
32 Wang Y, Dawson VL, Dawson TM. Poly (ADP-ribose) signals to mitochondrial AIF: a key event in parthanatos. Exp Neurol 2009; 218(2):193-202.   DOI   ScienceOn
33 Jaggi AS, Singh N. Mechanisms in cancerchemotherapeutic drugs-induced peripheral neuropathy. Toxicology 2012;291(1-3):1-9.   DOI   ScienceOn
34 Wen X, Lin ZQ, Liu B, Wei YQ. Caspase-mediated programmed cell death pathways as potential therapeutic targets in cancer. Cell Prolif 2012; 45(3):217-24.   DOI   ScienceOn
35 Muşat M, Vax VV, Borboli N, Gueorguiev M, Bonner S, Korbonits M. Cell cycle dysregulation in pituitary oncogenesis. Front Horm Res 2004; 32:34-62.   DOI
36 2009년 국가암등록통계 참고자료. 보건복지부. 2010.
37 Schulte-Hermann R, Bursch W, Kraupp-Grasl B, Oberhammer F, Wagner A, Jirtle R. Cell proliferation and apoptosis in normal liver and preneoplastic foci. Environ Health Perspect 1993; 101 Suppl 5:87-90.   DOI
38 Heeres JT, Hergenrother PJ. Poly(ADP-ribose) makes a date with death. Curr Opin Chem Biol 2007;11(6):644-53.   DOI   ScienceOn
39 Paoluzzi L, O'Connor OA. Targeting survival pathways in lymphoma. Adv Exp Med Biol 2010;687:79-96.   DOI