Aristolochia longa aqueous extract triggers the mitochondrial pathway of apoptosis in BL41 Burkitt’s lymphoma cells
DOI:
https://doi.org/10.22377/ijgp.v6i1.237Abstract
Aristolochia longa (from the family Aristolochiaceae) is widely used for cancer treatment in Algerian traditional medicine. The aim of the present study was to investigate the cytotoxic and apoptogenic activities. The phytochemical composition and acute toxicity of aqueous extracts of the roots of A. longa from Algeria. An aqueous extract (decoction) of dried A. longa roots was prepared. The cytotoxic effects of this aqueous extract were then evaluated in Burkitt’s lymphoma BL41 cells, by flow cytometry. The induction of apoptosis was assessed in two corroborative assays: The propidium iodide staining of cell DNA and flow cytometry analyses of light scattering. Mitochondrialmembrane potential was investigated with the fluorescent dye DIOC6. The expression and activation of capases-3, -8 and -9 were assessed by Western blotting. Acute oral toxicity was evaluated with a test dose limited to 5000 mg/kg. Phytochemical screening of A. longa roots was performed with standard qualitative procedures. The aqueous extract of A. longa induced cell death in a dose-dependent manner. The IC50 of A. longa aqueous extract was estimated at about 15,63 μg/ml. The extract-induced apoptosis, a loss of mitochondrial membrane
potential and the activation of caspases-9 and -3 followed by PARP cleavage. A. longa could therefore be considered a promising source of novel treatments for Burkitt’s and other lymphomas.
Key words: Apoptosis, Aristolochia longa, Burkitt’s lymphoma BL41 cell lines, caspase, mitochondrial pathway
Downloads
References
Sharma H, Parihar L, Parihar P. Review on cancer and anticancerous
properties of some medicinal plants. J Med Plants Res 2011;5:1818-35.
Nawab A, Yunus M, Ali Mahdi A, Gupta S. Evaluation of
Anticancer Properties of Medicinal Plants from the Indian Sub-
Continent. Mol Cell Pharmacol 2011;3:21-9.
Cragg GM, Newman DJ. Plants as a source of anti-cancer agents.
J Ethnopharmacol 2005;100:72-9.
Sithranga Boopathy N, Kathiresan K. Anticancer drugs from
marine flora: An overview. J Oncol 2010;2010:214186.
Neinhuis C, Wanke S, Hilu KW, Müller K, Borsch T. Phylogeny
of Aristolochiaceae based on parsimony, likelihood and Bayesian
analyses of trnL-trnF sequences. Plant Syst Evol 2005;250:7-26.
González F, Esquivel HE, Murcia GA and Pabón-Mora N. Aristolochia
pentandra (Aristolochiaceae) in Colombia: Biogeographic
implications and proposed synapomorphies between the
pentandrous species of Aristolochia and its South American sister
group. Rev Aca Colom Cien 2010;34:467-78.
Yu JQ, Liao ZX, Cai XQ, Lei JC, Zouc GL. Composition,
antimicrobial activity and cytotoxicity of essential oils from
Aristolochia mollissima. Environ Toxicol Pharmacol 2007;23:162-7.
Graham JG, Quinn ML, Fabricant DS, Farnsworth NR. Plants used
against cancer - an extension of the work of Jonathan Hartwell.
Journal of Ethnopharmacol 2000;73:347-77.
De Tommasi N, Rastrelli L, De Simone F. New Aristoclam
glycosides from Aristolochia constricta. Nat Prod Lett 1998;11:263-70.
Pistelli L, Nieri E, Bilia AR, Marsili A, Morelli I. Further phenantrene
derivatives from Aristolochia rotunda. Int J Pharmacognosy
;33:362-6.
Kostalova D, Hrochova V, Pronayova N, Lesko J. Constituents of
Aristolochia-clematitis L. Chem Pap 1991;45:713-6.
Cherif HS, Saidi F, Boutoumi H, Rouibi A, Chaouia C. Identification
and characterization of some chemicals from Aristolochia longa L.
Agricultura 2009;3:76-82.
Saidi F, Cherif HS, Metidji H, Rouibia A, Chaouia C, Abdulhussain MS,
et al. In vitro multiplication by direct organogenesis of a medicinal
plant Aristolochia longa L. Agricultura 2009;3:53-66.
Saidi F, Cherif HS, Lazouri H, Aid K, Rouibi A, Bele C, Matea C.
Determination of the lipid compounds of Aristolochia Longa L. from
Algeria. Bull U Agr 2009;66:17-23.
Benzakour G, Benkirane N, Amrani M, Oudghiri M. Immunostimulatory
potential of Aristolochia longa L. induced toxicity on liver, intestine and
kidney in mice. J Toxicol Environ Health Sci 2011;3:214-22.
Schrantz N, Bourgeade MF, Mouhamad S, Leca G, Sharma S
Vazquez A. p38-mediated regulation of an Fas-associated death
domain protein-independent pathway leading to caspase-8
activation during TGFbeta-induced apoptosis in human Burkitt
lymphoma B cells BL41. Mol Biol Cell 2001;12:3139-51.
Clybouw C, Mchichi B, Mouhamad S, Auffredou MT,
Bourgeade MF, Sharma S, et al. Down-regulation of Bim
expression: Relationship to resistance to apoptosis. J Immunol
;175:2968-73.
El Mchichi B, Hadji A, Vazquez A and Leca G. p38 MAPK and MSK1
mediate caspase-8 activation in manganese-induced mitochondriadependent
cell death. Cell Death Differ 2007;14:1826-36.
Li J, Xia X, Ke Y, Nie H, Smith MA and Zhu X. Trichosanthin
induced apoptosis in HL-60 cells via mitochondrial and
endoplasmic reticulum stress signaling pathways. Biochim
Biophys Acta 2007;1770:1169-80.
Karlsson J, Øra I, Pörn-Ares I, Pahlman S. Arsenic trioxide-induced
death of neuroblastoma cells involves activation of Bax and does
not require p53. Clin Cancer Res 2004;10:3179-88.
Watanapokasin R, Jarinthanan F, Nakamura Y, Sawasjirakij N,
Jaratrungtawee A, Suksamrarn S. Effects of α-mangostin on
apoptosis induction of human colon cancer. World J Gastroenterol
;17:2086-95.
Robinson MM, Zhang X. The world medicines situation 2011,
traditional medicines: Global situation, issues and challenges.
Geneva: World Health Organization Press; 2011.
Huang ST, Yang RC, Yang LJ, Lee PN, Pang JH. Phyllanthus urinaria
triggers the apoptosis and Bcl-2 down-regulation in Lewis lung
carcinoma cells. Life Sci 2003;72:1705-16.
Hamsa TP, Kuttan J. Harmine activates intrinsic and extrinsic
pathways of apoptosis in B16F-10 melanoma. Chin Med
;6:11.
Liu Z, Cheng M, Cao MZ. Potential targets for molecular imaging of
apoptosis resistance in hepatocellular carcinoma. Biomed Imaging
Interv J 2011;7:e5.
Samm N, Werner K, Rückert F, Saeger HD, Grützmann R,
Pilarsky C. The role of apoptosis in the pathology of pancreatic
cancer. Cancer 2011;3:1-16.
Dai Y, Lawrence TS, Xu L. Overcoming cancer therapy resistance
by targeting inhibitors of apoptosis proteins and nuclear factor
kappa B. Am J Transl Res 2009;1:1-15.
Fulda S. Evasion of apoptosis as a cellular stress response in cancer.
Int J Cell Biol 2010;2010:370835.
Reed JC, Pellecchia M. Apoptosis-based therapies for hematologic
malignancies. Blood 2005;106:408-18.
Cichorek M. Mechanisms of tumor cell’s ability to avoid apoptosis.
Dermatologia 2008;10:1-9.
Wu J, Liu T, Xie J, Xin F, Guo L. Mitochondria and calpains mediate
caspase-dependent apoptosis induced by doxycycline in HeLa
cells. Cell Mol Life Sci 2006;63:949-57.
Yang HL, Chen SC, Chen CS, Wang SY, Hseu YC. Alpinia pricei
rhizome extracts induce apoptosis of human carcinoma KB cells
via a mitochondria-dependent apoptotic pathway. Food Chem
Toxicol 2008;46:3318-24.