Full Paper View Go Back
Ashok Kumar1 , Anupama Mahajan2 , Zarina Begum3
- Department of Biotechnology, Punjab Technical University, Jalandhar, Kapurthala. India.
- Department of Biotechnology, Saheed Udham Singh College of Engineering & Technology, Mohali (PB), India.
- Department of Biotechnology, Saheed Udham Singh College of Engineering & Technology, Mohali (PB), India.
Correspondence should be addressed to: ashoka.kumar2007@rediff.com.
Section:Research Paper, Product Type: Journal-Paper
Vol.6 ,
Issue.1 , pp.128-134, Feb-2019
CrossRef-DOI: https://doi.org/10.26438/ijsrbs/v6i1.128134
Online published on Feb 28, 2019
Copyright © Ashok Kumar, Anupama Mahajan, Zarina Begum . This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
View this paper at Google Scholar | DPI Digital Library
How to Cite this Paper
- IEEE Citation
- MLA Citation
- APA Citation
- BibTex Citation
- RIS Citation
IEEE Style Citation: Ashok Kumar, Anupama Mahajan, Zarina Begum, “Mode of p38 and Nf-kβ Signalling Pathway on Induction of Apoptosis in Response to Flavonoids of Aloe Vera in Glioblastoma,” International Journal of Scientific Research in Biological Sciences, Vol.6, Issue.1, pp.128-134, 2019.
MLA Style Citation: Ashok Kumar, Anupama Mahajan, Zarina Begum "Mode of p38 and Nf-kβ Signalling Pathway on Induction of Apoptosis in Response to Flavonoids of Aloe Vera in Glioblastoma." International Journal of Scientific Research in Biological Sciences 6.1 (2019): 128-134.
APA Style Citation: Ashok Kumar, Anupama Mahajan, Zarina Begum, (2019). Mode of p38 and Nf-kβ Signalling Pathway on Induction of Apoptosis in Response to Flavonoids of Aloe Vera in Glioblastoma. International Journal of Scientific Research in Biological Sciences, 6(1), 128-134.
BibTex Style Citation:
@article{Kumar_2019,
author = {Ashok Kumar, Anupama Mahajan, Zarina Begum},
title = {Mode of p38 and Nf-kβ Signalling Pathway on Induction of Apoptosis in Response to Flavonoids of Aloe Vera in Glioblastoma},
journal = {International Journal of Scientific Research in Biological Sciences},
issue_date = {2 2019},
volume = {6},
Issue = {1},
month = {2},
year = {2019},
issn = {2347-2693},
pages = {128-134},
url = {https://www.isroset.org/journal/IJSRBS/full_paper_view.php?paper_id=1100},
doi = {https://doi.org/10.26438/ijcse/v6i1.128134}
publisher = {IJCSE, Indore, INDIA},
}
RIS Style Citation:
TY - JOUR
DO = {https://doi.org/10.26438/ijcse/v6i1.128134}
UR - https://www.isroset.org/journal/IJSRBS/full_paper_view.php?paper_id=1100
TI - Mode of p38 and Nf-kβ Signalling Pathway on Induction of Apoptosis in Response to Flavonoids of Aloe Vera in Glioblastoma
T2 - International Journal of Scientific Research in Biological Sciences
AU - Ashok Kumar, Anupama Mahajan, Zarina Begum
PY - 2019
DA - 2019/02/28
PB - IJCSE, Indore, INDIA
SP - 128-134
IS - 1
VL - 6
SN - 2347-2693
ER -
Abstract :
The phytochemical, Flavonoid has been shown apoptosis by numerous studies of cancer cell lines. Here, we have investigated the role of flavonoids of Aloe vera in regulation of apoptosis through p38 and Nf-kβ gene against human glioma-U87MG cells in vitro. The potential invasion of flavonoid on human glioma-U-87MG cells was examined by MTT assay and DNA fragmentation assay and expression of p38 and Nf-kβ gene was analysed by RT-PCR. Flavonoids significantly suppressed the apoptosis with IC50 113.29±0.5µg/ml and confirmed by DNA fragmentation assay. The results suggest that flavonoids induce apoptosis with decreased expression of p38 and Nf-kβ gene and protein analysis with SDS-PAGE. Assessments of cell viability represent that U-87MG cells were very sensitive to flavonoids and indicating DNA and protein synthesis delayed. In conclusion, flavonoids of Aloe showed inhibitory effect on Glioblastoma a brain tumor cells by apoptosis through regulation of p38 and Nf-kβ pathway at transcription and post –transcription level.
Key-Words / Index Term :
Glioblastoma, Aloe vera, Flavonoids, p38, Nf-kβ, U-87MG cell lines, RT-PCR, SDS-PAGE.
References :
[1]. De Angelis LM “Brain tumors” N Engl J Med 344:114–123, 2001. doi:10.1056/NEJM200101113440207
[2]. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, “The 2007 WHO classification of tumours of the central nervous system.” Acta Neuropathol 114: 97–109, 2007.
[3]. Wen PY, Kesari S “Malignant gliomas in adults.” N Engl J Med 359: 492– 507, 2008.
[4]. Wei J, Gabrusiewicz K, Heimberger A “The controversial role of microglia in malignant gliomas” Clinical & developmental immunology”, 285-246 , 2013.
[5]. Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, “Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma” The New England journal of medicine 352: 987–996, 2005.
[6]. Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, “Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial”. The lancet oncology 10: 459–466, 2009.
[7]. Rock K, McArdle O, Forde P, Dunne M, Fitzpatrick D, “A clinical review of treatment outcomes in glioblastoma multiforme–the validation in a non-trial population of the results of a randomised Phase III clinical trial: has a more radical approach improved survival?” The British journal of radiology 85: e729–733, 2012.
[8]. Yagi A, Kabash A, Okamura N, Haraguchi H, Moustafa SM, Khalifa TI. “Antioxidant, free radical scavenging and anti-inflammatory effects of aloes in derivatives in Aloe vera” Planta Med, 68(11):957–60, 2002.
[9]. Pugh N, Ross SA, ElSohly MA, Pasco DS. “Characterization of Aloeride, a new high -molecular-weight polysaccharide from Aloe vera with potent immunostimulatory activity” J Agric Food Chem 49(2):1030–4, 2001.
[10]. Fishman DA and Schwartz PE: “Current approaches to diagnosis and treatment of ovarian germ cell malignancies”. Curr Opin Obstet Gynecol 6: 98-104, 1994.
[11]. Pecere T, Gazzola MV, Mucignat C, Parolin C, Vecchia FD, Cavaggioni A. “Aloe-emodin is a new type of anticancer agent with selective activity against neuroectodermal tumors” Cancer Res 60: 2800-4, 2000.
[12]. Rodrigueg J, Yanez J, Vicente V, Alcaraz M, Benavente-García O, Lazona JA, “Effects of several flavonoids on the growth of B16f10 and SKMEL- 1 melanoma cell lines: Relationship between structure and activity” Melanoma Res 12:99-107, 2002.
[13]. Yonehara A, Tanaka Y, Kulkeaw K, Era T, Nakanishi Y, Sugiyama D. “Aloe vera Extract Suppresses Proliferation of Neuroblastoma Cells In Vitro” Anticancer Res 35(8):4479–85, 2015.
[14]. Xiao, B. X.; Guo, J. M.; Liu, D.H.; Zhang, S. “Aloe-emodin induces in vitro G2/M arrest and alkaline phosphatase activation in human oral cancer KB cells” Oral Oncol., 43, 905. 2007,
[15]. Fishman DA and Schwartz PE: “Current approaches to diagnosis and treatment of ovarian germ cell malignancies” Curr Opin Obstet Gynecol 6: 98-104, 1994.
[16]. Birt DF, Hendrich S and Wang W, “Dietary agents in cancer prevention: Flavonoids and isoflavonoids” Pharmacol Ther 90:157-177, 2001.
[17]. Lee FS, Hagler J, Chen ZJ, Maniatis T “Activation of the IkappaB alpha kinase complex by MEKK1, a kinase of the JNK pathway” Cell, 88:213–22, 1997.
[18]. Schwenger P, Alpert D, Skolnik EY, Vilcek J, “Activation of p38 mitogen-activated protein kinase by sodium salicylate leads to inhibition of tumor necrosis factor-induced IkBa phosphorylation and degradation” Mol Cell Biol; 18:78–84, 1998.
[19]. Beyaert R, Cuenda A, Vanden Berghe W, Plaisance S, Lee JC, Haegeman G,“The p38/ERK mitogen-activated protein kinase pathway regulates interleukin-6 synthesis response to tumor necrosis factor” EMBO J; 15:1914–23, 1996.
[20]. Vanden Berghe W, Plaisance S, Boone E, De Bosscher K, Schmitz ML, Fiers W. “p38 and extracellular signal-regulated kinase mitogen-activated protein kinase pathways are required for nuclear factor-kappa B p65 transactivation mediated by tumor necrosis factor” J Biol Chem; 273:3285–90, 1998.
[21]. Wang D, Baldwin AJ, “Activation of nuclear factor-kappa B-dependent transcription by tumor necrosis factor-alpha is mediated through phosphorylation of RelA/p65 on serine 529” J Biol Chem; 273:29411–6, 1998.
[22]. Naldini, A.; Carraro, F, “Role of inflammatory mediators in angiogenesis” Curr. Drug Targets Inflamm. Allergy, 4, 3–8, 2005.
[23]. Goldberg, J.E.; Schwertfeger, K.L. “Proinflammatory cytokines in breast cancer: Mechanisms of action and potential targets for therapeutics” Curr. Drug Targets, 11, 1133–1146, 2010.
[24]. Carter AB, Knudtson KL, Monick MM, Hunninghake GW, “The p38 Mitogen-activated Protein Kinase Is Required for NF-κB-dependent Gene Expression” J Biol Chem ; 274:30858–63, 1999.
[25]. G. R. Waller, S. Mangiafico† and C. R. Ritchey “A Chemical Investigation of Aloe Barbadensis Miller” Proc. Okla. Acad. Sci. 58: 69-76, 1978.
[26]. Miyuki Tanaka, Eriko Misawa, Yousuke Ito, Noriko Habara, Kouji Nomaguchi, Muneo Yamada, Tomohiro Toida, Hirotoshi Hayasawa, Mitunori Takase, Masanori Inagaki, And Ryuuichi Higuchi “Identification of Five Phytosterols from Aloe Vera Gel as Anti-diabetic Compounds” Biol. Pharm. Bull. 29(7) 1418—1422, 2006.
[27]. Hsu, S. L.; Yin, S. C.; Liu, M. C.; Reichert, U.; Ho, W. L. “Involvement of cyclin-dependent kinase activities in CD437-induced apoptosis” Exp. Cell Res., 252, 332, 1999.
[28]. Sambrook, J., Fritsch, E.F., and Maniatis, T. “Molecular Cloning. A Laboratory manual” Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, 1989.
[29]. Araya R, Takahashi R, Nomura Y, “Yeast two-hybrid screening using constitutive–active caspase-7 as bait in the identification of PA28gamma as an effector caspase substrate” Cell Death Differ , 9:322–8, 2002.
[30]. Xie J, Guo Q, Zhu H, Wooten M, Mattson M, “Protein kinase Ciota protects neural cells against apoptosis induced by amyloid beta-peptide” Mol Brain Res, 82:107– 13, 2000.
[31]. Reynolds, T.; Dweck, A.C, “Aloe vera leaf gel: a review update” J. Ethnopharmacol., 68, 3, 1999.
[32]. Chidambaram, M.; Manavalan, R.; Kathiresan, K. “Nanotherapeutics to overcome conventional cancer chemotherapy limitations” J. Pharm. Pharm. Sci. 14, 67–77, 2011.
[33]. Bosetti C, Rossi M, McLaughlin JK, Negri E, Talamini R, Lagiou P, Montella M, Ramazzotti V, Franceschi S and LaVecchia C: “Flavonoids and the risk of renal cell carcinoma” Cancer Epidemiol Biomarkers Prev 16: 98-101, 2007.
[34]. Mijatovic, S.; Maksimovic-Ivanic, D.; Radovic, J.; Popadic, D.; Momcilovic, M.; Harhaji, L.; Miljkovic, D.; Trajkovic, V, “Aloe emodin prevents cytokine-induced tumor cell death: the inhibition of auto-toxic nitric oxide release as a potential mechanism” Cell Mol. Life Sci., 61, 1805, 2004.
[35]. Lam KH, Alex D, Lam IK, Tsui SK, Yang ZF and Lee SM, “Nobiletin, a polymethoxylated flavonoid from citrus, shows antiangiogenic activity in a zebrafish in vivo model and HUVEC in vitro model” J Cell Biochem 112: 3313-3321, 2011.
[36]. Van Uden P, Kenneth NS and Rocha S, “Regulation of hypoxiainducible factor-1α by NF-kappa B” Biochem J 412: 477-484, 2008.
[37]. Arafa SA, Zhu Q, Barakat BM, Wani G, Zhao Q, El-Mahdy MA and Wani AA, “Tangeretin sensitizes cisplatin-resistant human ovarian cancer cells through down-regulation of phosphoinositide 3-kinase/Akt signaling pathway” Cancer Res 69: 8910-8917, 2009.
[38]. Lee, H-Z; Lin, C-J; Yang, W-H; Leung, W-C; Chang, S-P, “Aloe-emodin induced DNA damage through generation of reactive oxygen species in human lung carcinoma cells” Cancer Lett., 239, 55, 2006.
[39]. Lee FS, Hagler J, Chen ZJ, Maniatis T, “Activation of the IkappaB alpha kinase complex by MEKK1, a kinase of the JNK pathway” Cell , 88:213–22, 1997.
[40]. Carter AB, Knudtson KL, Monick MM, Hunninghake GW, “The p38 mitogen-activated protein kinase is required for NF-kappa B-dependent gene expression. The role of TATA-binding protein (TBP)” J Biol Chem, 274:30858–63, 1999.
[41]. K.-S. Chun, Y.-J. Surh, “Signal transduction pathways regulating cyclooxygenase-2 expression: potential molecular targets for chemoprevention” Biochemical Pharmacology 68, 1089–1100, 2004.
[42]. Lam IK, Alex D, Wang YH, Liu P, Liu AL, Du GH and Lee SM, “In vitro and in vivo structure and activity relationship analysis of polymethoxylated flavonoids: Identifying sinensetin as a novel antiangiogenesis agent” Mol Nutr Food Res 56: 945-956, 2012.
[43]. Luo H, Rankin GO, Liu L, Daddysman MK, Jiang BH and Chen YC, “Kaempferol inhibits angiogenesis and VEGF expression through both HIF dependent and independent pathways in human ovarian cancer cells” Nutr Cancer 61: 554-563, 2009.
[44]. Forsythe JA, Jiang BH, Iyer NV, Agani F, Leung SW, Koos RD and Semenza GL,“Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1” Mol Cell Biol 16: 4604-4613, 1996.
You do not have rights to view the full text article.
Please contact administration for subscription to Journal or individual article.
Mail us at support@isroset.org or view contact page for more details.