The Effect of Seeds and Fruit Pulp of Adansonia digitata L. (Baobab) on Ehrlich Ascites Carcinoma

Fahmy G. Elsaid

Zoology Department, Faculty of Science, Mansoura University, Mansoura, Egypt;Biology Department, Science College, King Khalid University, Abha, KSA..

DOI: 10.4236/fns.2013.48A005                

Abstract

The anti-tumor effect of Adansonia digitata on Ehrlich ascites carcinoma cells (EAC) is still novel talk. This study is focusing on the role of the extracts of seeds and the fruit pulp of Adansonia on the antioxidants activity and the molecular changes of pro-apoptic and anti-apoptic genes expression before and after the treatment of EAC cells bearing mice. Adult female BALB/C mice were used in this study; subgrouped randomly into four groups: control group (non-tumorized); EAC tumorized group, mice was i.p. inoculated with 2.5 × 10⁶ of EAC cells; EAC+ extract of seeds group, tumorized mice was inoculated with 2.5 × 10⁶ of EAC cells and i.p. administered with the extract of Adansonia seeds (300 mg/kg b. wt.); EAC+ fruit pulp group, tumorized mice was inoculated with 2.5 × 10⁶ of EAC cells and i.p. administered with the extract of Adansonia fruit pulp (300 mg/kg b. wt.). The antioxidant enzymes were inhibited in EAC cells and in ascetic fluid of tumorized mice. Also the oxidative stress was increased significantly in EAC cells bearing mice. The liver was affected with the transplantation of EAC cells as reflected by the imbalance in the antioxidants and oxidants in the EAC cells bearing mice. Moreover, the molecular changes in p53 and B-cell lymphoma (Bcl-2) genes expression were recorded in EAC cells bearing mice. The extracts of adansonia have a promising role as antioxidant action due to their antioxidant effect as they ameliorate the imbalance in antioxidants and oxidants balance. The plant extract has anti-apoptosis role by restoring the P53 and Bcl-2 genes expression. Also the plant has antitumor action as they restore tumor markers levels such as α-l-fucosidase and arginase to the normal levels.

Keywords

Ehrlich Ascites Carcinoma; Tumor Markers; Antioxidants; Oxidative Stress; Gene Expression; Adansonia digitata; Baobab

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Ö Kaleoglu and N. Isli, “Ehrlich-Lettre Asit Tümorü,” Tip Fakültesi Mecmuasi, Vol. 40, No. 1, 1977, pp. 978984.
[2]	H. G. Okay, “Deneysel EAT Olu_turulan Fare Karaciger Plazmasinda Nitrik Oksit Metabolizmasinin Incelenmesi. Yüksek Lisans Tezi,” Istanbul üniversitesi Saglik Bilimleri Enstitüsü, Biyokimya ABD, Istanbul, 1998.
[3]	H. Gümüshan and I.P., I.V. ve S.C., “Yollarla Uygulanan Adriamycin’in Ehrlich Asit Tümorü (EAT) Tasiyan Farelere Etkileri üzerine Bir Calisma,” Harran üniversitesi Fen Bilimleri Enstitüsü, Yüksek Lisans Tezi, Sanliurfa, 2002.
[4]	Z. Song, J. Varani and I. J. Goldstein, “Differences in Cell Surface Carbohydrates, and in Laminin and Fibronectin Synthesis between Adherent and Non-Adherent Ehrlich Ascites Tumor Cells,” International Journal of Cancer, Vol. 55, No. 6, 1993, pp. 1029-1035. doi:10.1002/ijc.2910550625
[5]	Ö. Bulan, “Ehrlich Ascites Tümor Hücrelerinde Yaslanmaile Hücre Kinetigi Arasindaki Iliskiler,” YüksekLisans Tezi, Istanbulüniversitesi Fen Bilimleri Enstitüsü, Istanbul, 1990.
[6]	E. Aktas, Ehrlich Asit Sivisinin L-Hücrelerinin Cogalma Hizina Etkisi,” Yüksek Lisans Tezi, Istanbul üniversitesi Fen Bilimleri Enstitüsü, Istanbul, 1996.
[7]	M. Ozaslan, I. D. Karagoz, I. H. Kilic and M. E. Guldur, “Ehrlich Ascites Carcinoma,” African Journal of Biotechnology, Vol. 10, No. 13, 2011, pp. 2375-2378.
[8]	S. Altun, “Normal, Tümoralve Rejeneratif Büyümeler Arasindaki Kinetik Iliskiler,” Turkish Journal of Biology, Vol. 20, No. 3, 1996, pp. 153-173.
[9]	T. Andoh, P. B. Chock and C. C. Chiueh, “The Roles of Thioredoxin in Protection against Oxidative Stress-Induced Apoptosis in SH-SY5Y Cells,” The Journal of Biological Chemistry, Vol. 277, 2002, pp. 9655-9660. doi:10.1074/jbc.M110701200
[10]	M. R. Bleavins, D. A. Brott, J. D. Alvey and F. A. de la Iglesia, “Flow Cytometric Characterization of Lymphocyte Subpopulations in the Cynomolgus Monkey (Macaca fascicularis),” Veterinary Immunology and Immunopathology, Vol. 37, No. 1, 1993, pp. 1-13. doi:10.1016/0165-2427(93)90011-R
[11]	C. Lobo, M. A. Ruiz-Bellido, J. C. Aledo, J. Marquez, I. N. De Castro and F. J. Alonso, “Inhibition of Glutaminase Expression by Antisense mRNA Decreases Growth and Tumourigenicity of Tumour Cells,” Biochemical Journal, Vol. 348, 2000, pp. 257-261. doi:10.1042/0264-6021:3480257
[12]	M. A. El-Missiry, A. I. Othman, M. A. Amer and E. Mohamed, “Ottelione a Inhibited Proliferation of Ehrlich Ascites Carcinoma Cells in Mice,” Chemico-Biological Interactions, Vol. 200, No. 2-3, 2012, pp. 119-127. doi:10.1016/j.cbi.2012.10.013
[13]	D. Li, E. Ueta, T. Kimura, T. Yamamoto and T. Osaki, “Reactive Oxygen Species (ROS) Control the Expression of Bcl-2 Family Proteins by Regulating Their Phosphorylation and Ubiquitination,” Cancer Science, Vol. 95, No. 8, 2004, pp. 644-650. doi:10.1111/j.1349-7006.2004.tb03323.x
[14]	H. Xu, R. J. Steven and X. M. Li, “Dose-Related Effects of Chronic Antidepressants on Neuroprotective Proteins BDNF, Bcl-2 and Cu/Zn-SOD in Rat Hippocampus,” Neuropsychopharmacology, Vol. 28, 2003, pp. 53-62. doi:10.1038/sj.npp.1300009
[15]	T. Das, G. Sa, P. Sinha and P. K. Ray, “Induction of Cell Proliferation and Apoptosis: Dependence on the Dose of the Inducer,” Biochemical and Biophysical Research Communications, Vol. 260, No. 1, 1999, pp. 105-110. doi:10.1006/bbrc.1999.0712
[16]	G. Donati, L. Montanaro and M. Derenzini, “Ribosome Biogenesis and Control of Cell Proliferation: p53 Is Not Alone,” Cancer Research, Vol. 72, 2012, pp. 1602-1607. doi:10.1158/0008-5472.CAN-11-3992
[17]	T. Miyashita and J. C. Reed, “Tumor Suppressor p53 Is a Direct Transcriptional Activator of the Human Bax Gene,” Cell, Vol. 80, No. 2, 1995, pp. 293-299. doi:10.1016/0092-8674(95)90412-3
[18]	T. Miyashita, S. Krajewski, M. Krajewska, H. G. Wang, H. K. Lin, D. A. Liebermann, B. Hoffman and J. C. Reed, “Tumor Suppressor p53 Is a Regulator of Bcl-2 and Bax Gene Expression in Vitro and in Vivo,” Oncogene, Vol. 9, No. 6, 1994, pp. 799-1805.
[19]	D. H. Cho, T. N. Tomohiro, J. Fang, P. Cieplak, A. Godzik, Z. Gu and S. A. Lipton, “S-Nitrosylation of Drp1 Mediates β-Amyloid-Related Mitochondrial Fission and Neuronal Injury,” Science, Vol. 324, No. 5923, 2009, pp. 102105. doi:10.1126/science.1171091
[20]	X. R. Cheng, L. Zhang, J. J. Hu, L. Sun and G. H. Du, “Neuroprotective Effects of Tetramethylpyrazine on Hydrogen Peroxide-Induced Apoptosis in PC12 Cells,” Cell Biology International, Vol. 31, 2007, pp. 438-443. doi:10.1016/j.cellbi.2006.10.001
[21]	M. Ozaslan, I. D. Karagoz, M. E. Kalender, I. H. Kilic, I. Sari and A. Karagoz, “In Vivo Antitumoral Effect of Plantago major L. Extract on Balb/C Mouse with Ehrlich Ascites Tumor,” The American Journal of Chinese Medicine, Vol. 35, No. 5, 2007, pp. 841-851. doi:10.1142/S0192415X07005314
[22]	G. M. Cragg and D. J. Newman, “Discovery and Development of Antineoplastic Agents from Natural Sources,” Cancer Investigation, Vol. 17, No. 2, 1999, pp. 153-163.
[23]	G. P. P. Kamatou, I. Vermaak and A. M. Viljoen, “An Updated Review of Adansonia digitata: A Commercially Important African Tree,” South African Journal of Botany, Vol. 77, No. 4, 2011, pp. 908-919. doi:10.1016/j.sajb.2011.08.010
[24]	A. A. Al-Qarawi, M. A. Al-Damegh and S. A. El-Mougy, “Hepatoprotective Influence of Adansonia digitata Pulp,” Journal of Herbs Spices and Medicinal Plants, Vol. 10, No. 3, 2003, pp. 1-6. doi:10.1300/J044v10n03_01
[25]	C. Buchmann, S. Prehsler, A. Hartl and C. R. Vogl, “The Importance of Baobab (Adansonia digitata L.) in Rural West African Subsistence—Suggestion of a Cautionary Approach to International Market Export of Baobab Fruits,” Ecology of Food and Nutrition, Vol. 49, No. 3, 2010, pp. 145-172. doi:10.1080/03670241003766014
[26]	R. Addy, “Baobab Fruit Approved as Food Ingredient in US,” 2009. http://www.nutraingredientsusa.com/content/view/print/259574,2009.
[27]	A. C. Sanchez, P. E. Osborne and N. Haq, “Identifying the Global Potential for Baobab Tree Cultivation Using Ecological Niche Modeling,” Agroforestry Systems, Vol. 80, No. 2, 2010, pp. 191-201. doi:10.1007/s10457-010-9282-2
[28]	J. Gebauer, K. El-Siddig and G. Ebert, “Baobab (Adansonia digitata L.): A Review on a Multipurpose Tree with Promising Future in Sudan,” Gartenbauwissenschaft, Vol. 67, No. 4, 2002, pp. 155-160.
[29]	S. Vertuani, E. Braccioli, V. Buzzoni and V. S. Manfredini, “Antioxidant Capacity of Adansonia Digitata Fruit Pulp and Leaves,” Acta Phytotherapeutica, Vol. 5, No. 2, 2002, pp. 2-7.
[30]	A. A. Shahat, “Procyanidins from Adansonia digitata,” Pharmaceutical Biology, Vol. 44, No. 6, 2006, pp. 445450. doi:10.1080/13880200600798510
[31]	R. A. Mothana, U. Lindequist, R. Gruenert and P. J. Bednarski, “Studies of the in Vitro Anticancer, Antimicrobial and Antioxidant Potentials of Selected Yemeni Medicinal Plants from the Island Soqotra,” BMC Complementary & Alternative Medicine, Vol. 9, 2009, pp. 7-18. doi:10.1186/1472-6882-9-7
[32]	M. Nishikimi, N. A. Rao, et al., “The Occurrence of Superoxide Anion in the Reaction of Reduced Phenazine Methosulfate and Molecular Oxygen,” Biochemical and Biophysical Research Communications, Vol. 46, No. 2, 1972, pp. 849-854. doi:10.1016/S0006-291X(72)80218-3
[33]	G. L. Ellman, “Tissue Sulfhydryl Groups,” Archives of Biochemistry and Biophysics, Vol. 82, No. 1, 1959, pp. 70-77. doi:10.1016/0003-9861(59)90090-6
[34]	E. Beutler, O. Duron, B. M. Kelly, “Improved Method for the Determination of Blood Glutathione,” The Journal of Laboratory and Clinical Medicine, Vol. 61, No. 1, 1963, pp. 882-888.
[35]	H. Ohkawa, N. Ohishi, et al., “Assay for Lipid Peroxides in Animal Tissues by Thiobarbituric Acid Reaction,” Analytical Biochemistry, Vol. 95, No. 2, 1979, pp. 351358. doi:10.1016/0003-2697(79)90738-3
[36]	H. Aebi, “Catalase in Vitro,” Methods in Enzymology, Vol. 105, 1984, pp. 121-126. doi:10.1016/S0076-6879(84)05016-3
[37]	M. Walter and H. Gerade, “An Ultramicromethod for the Determination of Conjugated and Total Bilirubin in Serum or Plasma,” Microchemical Journal, Vol. 15, No. 2, 1970, pp. 231-243. doi:10.1016/0026-265X(70)90045-7
[38]	A. Lamien-Meda, C. E. Lamien, M. M. Y. Compaoré, R. N. T. Meda, M. Kiendrebeogo, B. Zeba, J. F. Millogo and O. G. Nacoulma, “Polyphenol Content and Antioxidant Activity of Fourteen Wild Edible Fruits from Burkina Faso,” Molecules, Vol. 13, No. 3, 2008, pp. 581-594. doi:10.3390/molecules13030581
[39]	M. Gupta, U. K. Mazumder, R. S. Kumar, T. Sivakumar and M. L. Vamsi, “Antitumor Activity and Antioxidant Status of Caesalpinia Bonducella against Ehrlich Ascites Carcinoma in Swiss Albino Mice,” Journal of Pharmacological Science, Vol. 94, 2004, pp. 177-184.
[40]	A. Lamien-Meda, C. E. Lamien, M. M. Compaoré, R. N. Meda, M. Kiendrebeogo, B. Zeba, J. F. Millogo and O. G. Nacoulma, “Polyphenol Content and Antioxidant Activity of Fourteen Wild Edible Fruits from Burkina Faso,” Molecules, Vol. 13, No. 3, 2008, pp. 581-594. doi:10.3390/molecules13030581
[41]	L. Nhukarume, Z. Chikwambi, M. Muchuweti and B. Chipurura, “Phenolic Content and Antioxidant Capacities of Parinari curatelifolia, Strychnos spinosa and Adansonia digitata,” Journal of Food Biochemistry, Vol. 34, Suppl. 1, 2008, pp. 207-221. doi:10.1111/j.1745-4514.2009.00325.x
[42]	N. Senthilkumar, S. Badami, S. H. Dongre and S. Bhojraj, “Antioxidant and Hepatoprotective Activity of the Methanol Extract of Careya arborea Bark in Ehrlich Ascites Carcinoma-Bearing Mice,” Journal of Natural Medicines, Vol. 62, No. 3, 2008, pp. 336-339. doi:10.1007/s11418-008-0237-0
[43]	C. P. Rubbi and J. Milner, “P53: Guardian of a Genome’s Guardian? Cell Cycle, Vol. 2, No. 1, 2003, pp. 20-21. doi:10.4161/cc.2.1.297
[44]	M. P. Mattson, “Apoptosis in Neurodegenerative Disorders,” Nature Reviews. Molecular Cell Biology, Vol. 1, No. 2, 2000, pp. 120-129. doi:10.1038/35040009
[45]	R. B. Petersen, A. Nunomura, H. G. Lee, G. Casadesus, G. Perry, M. A. Smith and X. Zhu, “Signal Transduction Cascades Associated with Oxidative Stress in Alzheimer’s Disease,” Journal of Alzheimer’s Disease, Vol. 11, No. 2, 2007, pp. 143-152.