Middle East Journal of Cancer

Fagonia Arabica Extract Exerts Antitumor Effect on Mice Bearing Ehrlich Carcinoma

Document Type : Original Article(s)

Authors

Sanaa A. El-Benhawy 1
Salama M. EL-Darier 2
Samia A. Ebeid 3
Samar S. Elblehi 4
Sabbah I. Hammoury 5
Mai H. El-Sheikh 3

1 Department of Radiation Sciences, Medical Research Institute, Alexandria University, Alexandria, Egypt

2 Department of Botany and Microbiology, Faculty of Science, Alexandria University, Alexandria, Egypt

3 Department of Applied Medical Chemistry, Medical Research Institute, Alexandria University, Alexandria, Egypt

4 Department of Pathology, Faculty of Veterinary Medicine, Alexandria University, Alexandria, Egypt

5 Medical Physics and Radiotherapy Department, Ayadi Almostakbal Oncology Center, Alexandria, Egypt

https://doi.org/10.30476/mejc.2021.86945.1377
Abstract
Background: To date, no studies have investigated the anticancer potential of Fagonia arabica. we aimed to investigate the antitumor potentiality and radiosensitizing effect of Fagonia arabica ethanolic extract (FAEE) on mice bearing solid ehrlich carcinoma (EC).
Method: This experimental animal study included 80 Balb-c mice and divided them into four groups: Group I: 10 EC-bearing mice as untreated controls; Group II: 10 EC-bearing mice exposed to a single dose of ionizing radiation (IR) at tumor localization (6Gy); Group III: 30 EC-bearing mice, each 10 mice received different dose of FAEE (250, 500, and 1000 mg/kg/day); Group IV: 30 EC-bearing mice, each 10 mice received different dose of FAEE (250, 500, and 1000 mg/kg/day) plus a single dose of IR (6Gy). P-FOXO3a and p-AKT levels were measured in tumor tissue homogenate via ELISA technique. BCL-2 gene expression was assessed with realtime polymerase chain reaction. Tumor tissues were stained with haematoxylin and eosin stain and examined.
Results: FAEE has antiproliferative effect on EC-bearing mice reflected by the decrease in tumor volume and tumor growth rate in a dose-dependent manner. Combination of FAEE with IR significantly increased radiation-induced tumor damage in comparison with IR alone. We observed a significant decrease in the concentration of p-AKT and p-FOXO3a and down-regulation of BCL-2 gene in the EC-bearing mice treated with FAEE only or in combination with IR.
Conclusion: FAEE may be an effective antitumor agent against breast cancer. FAEE exerts radio-sensitizing effect, especially at a dose of 500 mg/kg. FAEE interferes with the apoptosis process via decreasing p-AKT and p-FOXO3a and down-regulation of BCL-2 gene.

Keywords

Fagonia arabica
Ionizing
Radiation
Ehrlich tumor
p-FOXO3a
p-AKT

How to cite this article:

El- Benhawy SA, EL-Darier SM, Ebeid SA, Elblehi SS, Hammoury SI, El-Sheikh MH. Fagonia arabica extract exerts antitumor effect on mice bearing Ehrlich carcinoma. Middle East J Cancer. 2022;13(2):324-36. doi: 10.30476/mejc.2021.86945. 1377.

  1. Azubuike SO, Muirhead C, Hayes L, McNally R. Rising global burden of breast cancer: the case of sub-Saharan Africa (with emphasis on Nigeria) and implications for regional development: a review. World J Surg Oncol. 2018;16(1):63. doi:10.1186/s12957-018-1345-2.
  2. Sharma R. Breast cancer incidence, mortality and mortality-to-incidence ratio (MIR) are associated with human development, 1990–2016: evidence from Global Burden of Disease Study 2016. Breast Cancer. 2019;26(4):1-18.
  3. Unger-Saldaña K. Challenges to the early diagnosis and treatment of breast cancer in developing countries. World J Clin Oncol. 2014;5(3):465-77.
  4. Qiao J, Liu Z, Fu YX. Adapting conventional cancer treatment for immunotherapy. J Mol Med (Berl). 2016;94(5):489-95.
  5. Baskar R, Dai J, Wenlong N, Yeo R, Yeoh KW. Biological response of cancer cells to radiation treatment. Front Mol Biosci. 2014;1:24. doi:10.3389/fmolb.2014.00024.
  6. Wang Z, Wang N, Chen J, Shen J. Emerging glycolysis targeting and drug discovery from chinese medicine in cancer therapy. Evid Based Complement Alternat Med. 2012;2012:873175. doi: 10.1155/2012/873175.
  7. Hematulin A, Ingkaninan K, Limpeanchob N, Sagan D. Ethanolic extract from Derris scandens Benth mediates radiosensitzation via two distinct modes of cell death in human colon cancer HT-29 cells. Asian Pac J Cancer Prev. 2014;15(4):1871-7.
  8. Franke TF, Hornik CP, Segev L, Shostak GA, Sugimoto C. PI3K/Akt and apoptosis: size matters. Oncogene. 2003;22(56):8983-98.
  9. Guo JP, Tian W, Shu S, Xin Y, Shou C, Cheng JQ. IKBKE phosphorylation and inhibition of FOXO3a: a mechanism of IKBKE oncogenic function. PLoS One. 2013;8(5):e63636.
  10. Farhan M, Wang H, Gaur U, Little PJ, Xu J, Zheng W. FOXO signaling pathways as therapeutic targets in cancer. Int J Biol Sci. 2017;13(7):815-27.
  11. Zhang X, Tang N, Hadden TJ, Rishi AK. Akt, FoxO and regulation of apoptosis. Biochim Biophys Acta. 2011;1813(11):1978-86.
  12. Habashy HO, Rakha EA, Aleskandarany M, Ahmed MA, Green AR, Ellis IO, et al. FOXO3a nuclear localisation is associated with good prognosis in luminal-like breast cancer. Breast Cancer Res Treat. 2011;129(1):11-21.
  13. Lu M, Xiang J, Xu F, Wang Y, Yin Y, Chen D. The expression and significance of pThr32-FOXO3a in human ovarian cancer. Med Oncol. 2012;29(2):1258-64. doi: 10.1007/s12032-011-9919-7.
  14. Puri D, Bhandari A. Fagonia: A potential medicinal desert plant. JNPA. 2015;27(1):28-33. doi:10.3126/jnpa.v27i1.12147.
  15. Shehab NG, Mahdy A, Khan SA, Noureddin SM. Chemical constituents and biological activities of Fagonia indica Burm F. Res J Med Plant. 2011;5(5):531-46.
  16. Satpute R, Bhattacharya R, S Kashyap R, J Purohit H, Y Deopujari J, M Taori G, et al. Antioxidant potential of Fagonia arabica against the chemical ischemia induced in PC12 cells. Iran J Pharm Res. 2012;11(1):303-13.
  17. Azam F, Sheikh N, Ali G, Tayyeb A. Fagonia indica repairs hepatic damage through expression regulation of toll-like receptors in a liver injury model. J Immunol Res. 2018;2018:7967135. doi: 10.1155/2018/7967135.
  18. Senthil Kumar R, Rajkapoor B, Perumal P, Dhanasekaran T, Alvin Jose M, Jothimanivannan C. Antitumor activity of Prosopis glandulosa Torr. On Ehrlich ascites carcinoma (EAC) tumor bearing mice. Iran J Pharm Res 2011;10(3): 505-10.
  19. Ferreira E, da Silva AE, Serakides R, Gomes MG, Cassali GD. Ehrlich tumor as model to study artificial hyperthyroidism influence on breast cancer. Pathol Res Pract. 2007; 203(1):39-44.
  20. Bancroft JD, Gamble M. The hematoxylin and eosin. In: Suvarna SK, Layton c, Bancroft JD, editors. Theory and Practice of Histochemical techniques. 2013. 7th Churchill Livingstone, Edinburgh, New York.p.179-220.
  21. Sisto M, Lisi S. Saponins from Tribulus Terrestris Linn plant: Potentials and challenges for prevention of solar ultraviolet radiation-induced damages and malignant transformation. Biomed J Sci & Tech Res. 2019;16(5): 12345-52. doi:10.26717/BJSTR.2019.16.002911.
  22. Moding, EJ, Kastan MB, Kirsch DG. Strategies for optimizing the response of cancer and normal tissues to radiation. Nat Rev Drug Discov. 2013;12(7):526-42.
  23. Jagetia GC, Venkatesha VA. Enhancement of radiation effect by Aphanamixis polystachya in mice transplanted with Ehrlich ascites carcinoma. Biol Pharm Bull. 2005;28(1):69-77.
  24. Lam M, Carmichael AR, Griffiths HR. An aqueous extract of Fagonia cretica induces DNA damage, cell cycle arrest and apoptosis in breast cancer cells via FOXO3a and p53 expression. PLoS One. 2012; 7(6):e40152.
  25. Patel A, Soni A, Siddiqi NJ, Sharma P. An insight into the anticancer mechanism of Tribulus terrestris extracts on human breast cancer cells. 3 Biotech. 2019;9(2):58. doi: 10.1007/s13205-019-1585-z.
  26. Hashemi Sheikh Shabani S, Seyed Hasan Tehrani S, Rabiei Z, Tahmasebi Enferadi S, Vannozzi GP. Peganum harmala L.'s anti-growth effect on a breast cancer cell line. Biotechnol Rep (Amst). 2015;8:138-43.
  27. Qi F, Li A, Inagaki Y, Gao J, Li J, Kokudo N, et al. Chinese herbal medicines as adjuvant treatment during chemoor radio-therapy for cancer. Biosci Trends. 2010;4(6):297-307.
  28. Mao XM, Zhou P, Li SY, Zhang XY, Shen JX, Chen QX, et al. Diosgenin suppresses cholangiocarcinoma cells via inducing cell cycle arrest and mitochondriamediated apoptosis. Onco Targets Ther. 2019;12:9093-104. doi:10.2147/OTT.S226261.
  29. Castaneda CA, Cortes-Funes H, Gomez HL, Ciruelos EM. The phosphatidyl inositol 3-kinase/AKT signaling pathway in breast cancer. Cancer Metastasis Rev. 2010; 29(4): 751-9.
  30. Tzivion G, Dobson M, Ramakrishnan G. FoxO transcription factors; Regulation by AKT and 14-3-3 proteins. Biochim Biophys Acta. 2011; 1813(11):1938-45.
  31. Zhang XF, Sun RQ, Jia YF, Chen Q, Tu RF, Li KK, et al. Synthesis and mechanisms of action of novel harmine derivatives as potential antitumor agents. Sci Rep. 2016;6:33204. doi: 10.1038/srep33204.
  32. Waheed A, Barker J, Barton SJ, Owen CP, Ahmed S, Carew MA. A novel steroidal saponin glycoside from Fagonia indica induces cell-selective apoptosis or necrosis in cancer cells. Eur J Pharm Sci. 2012;47(2):464-73.
  33. Kurutas EB. The importance of antioxidants which play the role in cellular response against oxidative/nitrosative stress: current state. Nutr J. 2016;15(1):71.
  34. Barrera G. Oxidative stress and lipid peroxidation products in cancer progression and therapy. ISRN Oncol. 2012;2012:137289. doi:10.5402/2012/137289.
  35. McGill MR. The past and present of serum aminotransferases and the future of liver injury biomarkers. Excli j. 2016;15:817-28.
  36. Aldubayan MA, Elgharabawy RM, Ahmed AS, Tousson E. Antineoplastic activity and curative role of avenanthramides against the growth of ehrlich solid tumors in mice. Oxid Med Cell Longev. 2019;2019:5162687. doi: 10.1155/2019/5162687.
  37. Tousson E, Hafez E, Abo Gazia MM, Salem SB, Mutar TF. Hepatic ameliorative role of vitamin B17 against Ehrlich ascites carcinoma-induced liver toxicity. Environ Sci Pollut Res Int. 2020;27(9):9236-46. doi:10.1007/s11356-019-06528-6.
  38. Bagban I, Roy S, Chaudhary A, Das S, Gohil K, Bhandari K. Hepatoprotective activity of the methanolic extract of Fagonia indica Burm in carbon tetra chloride induced hepatotoxicity in albino rats. Asian Pac J Trop Biomed. 2012; 2: S1457–S1460.

Home

Guide for Authors

Submit Manuscript

Guide for Reviewers

Contact Us