ABSTRACT:
Background: Breast cancer has the highest occurrence among women worldwide. It is listed as the fifth top cause of mortality due to cancer. There is no effective therapy till now for metastatic stages. Objective: Study of the effect of metformin and/or omega-3 on DMBA-induced BC development in Albino Wistar rats. Methods: The study included 30 female rats, separated into five groups: a normal control group (C), a pathological control group (BC), Metformin group (M), Omega-3 group (O), and Combination group (M+O). The mammary glands were excised immediately after sacrifice to determine the histological type and grade of the tumors. Both malondialdehyde levels and catalase activity in the mammary glands were assayed as indicators of oxidative stress and the percentage of body weight gain was calculated. Results: Invasive ductal carcinoma formed in the (BC) group and the highest proportion of aggressive tumors was observed in this group, where the grade of the tumors ranged between grade III and II. The incidence of invasion decreased in the Metformin group by 83.33%, in the Omega-3 group by 33.33% and in the Combination group by 100%. The tumors that formed in the treatment groups exhibited lower aggressiveness in comparison to those observed in the (BC) group. Malondialdehyde levels increased, catalase activity in the mammary glands decreased and the percentage of body weight gain decreased in the (BC) group in comparison to the (C) group. While malondialdehyde levels decreased, catalase activity in the mammary glands increased and the percentage of body weight gain increased in the treatment groups in comparison to the (BC) group. Conclusion: Metformin has shown its capacity to delay the development of breast tumors and decrease their aggressiveness, while omega-3 has shown the ability to reduce the aggressiveness of tumors. Their combination also delayed the development of breast tumors and controlled their aggressiveness, but there was no statistical difference compared to metformin or omega-3 alone.
Cite this article:
Noor Baddour, Ahmad Al Manadili, Ramez Wannous. Evaluation the effect of Metformin and/or Omega-3 on the Development of Breast Cancer in Albino Wistar Rats. Research Journal Pharmacy and Technology. 2025;18(8):3606-2. doi: 10.52711/0974-360X.2025.00519
Cite(Electronic):
Noor Baddour, Ahmad Al Manadili, Ramez Wannous. Evaluation the effect of Metformin and/or Omega-3 on the Development of Breast Cancer in Albino Wistar Rats. Research Journal Pharmacy and Technology. 2025;18(8):3606-2. doi: 10.52711/0974-360X.2025.00519 Available on: https://www.rjptonline.org/AbstractView.aspx?PID=2025-18-8-22
REFERENCES:
1. Raya A, Hussein F, Kamis A. The Prognostic value of Serum Ferritin in Breast cancer patients. Res J Pharm Technol. 2022; 15(9): 3975-3979. doi:10.52711/0974-360X.2022.00666
2. Karnam KC, Ellutla M, Bodduluru LN, et al. Preventive effect of berberine against DMBA-induced breast cancer in female Sprague Dawley rats. Biomed Pharmacother. 2017; 92: 207-214. doi:10.1016/j.biopha.2017.05.069
3. Alshafie M, Soqia J, Alhomsi D, Alameer MB, Yakoub - Agha L, Saifo M. Knowledge and practice of breast self-examination among breast cancer patients in Damascus, Syria. BMC Womens Health. 2024; 24(1): 1-9. doi:10.1186/s12905-024-02912-8
4. Jayashree V, Velraj M. Breast Cancer and various Prognostic Biomarkers for the diagnosis of the disease: A Review. Res J Pharm Technol. 2017; 10(9): 3211-3216. doi:10.5958/0974-360X.2017.00570.4
5. Suresh R, Benitojohnson D, Maheswari C, Venkatnarayanan R, Manavalan R. Chemo Preventive Activity of Triumfetta rhomboidea in 7, 12-Dimethylbenz (A) Anthracene Induced Breast Cancer in Sprague-Dawley Rat Model . Res J Pharm Technol. 2017;10(3):687. doi:10.5958/0974-360X.2017.00128.7
6. Mehraban F, Mostafazadeh M, Sadeghi H, et al. Anticancer activity of Astragalus ovinus against 7, 12 dimethyl benz (a) anthracene (DMBA)-induced breast cancer in rats. Avicenna J Phytomedicine. 2020; 10(5): 533-545. http://www.ncbi.nlm.nih.gov/pubmed/32995331%0Ahttp://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC7508319
7. Emam KK, Abdel Fattah ME, El Rayes SM, Hebishy MA, Dessouki AA. Assessment of Wheat Germ Oil Role in the Prevention of Induced Breast Cancer in Rats. ACS Omega. 2022; 7(16): 13942-13952. doi:10.1021/acsomega.2c00434
8. Sabaa M, Sharawy MH, El-Sherbiny M, Said E, Salem HA, Ibrahim TM. Canagliflozin interrupts mTOR-mediated inflammatory signaling and attenuates DMBA-induced mammary cell carcinoma in rats. Biomed Pharmacother. 2022; 155: 113675. doi:10.1016/j.biopha.2022.113675
9. Nassan MA, Soliman MM, Ismail SA, El-Shazly S. Effect of Taraxacum officinale extract on PI3K/Akt pathway in DMBA-induced breast cancer in albino rats. Biosci Rep. 2018; 38(6): 1-20. doi:10.1042/BSR20180334
10. Costa E, Ferreira-Gonçalves T, Chasqueira G, Cabrita AS, Figueiredo I V., Reis CP. Experimental models as refined translational tools for breast cancer research. Sci Pharm. 2020; 88(3): 1-29. doi:10.3390/scipharm88030032
11. Maysarah H, Faradilla M, Sari I, Illian DN. Cancer Chemopreventive effect of Rodent Tuber (Typhonium flagelliforme (Lood) Bl) against DMBA-Induced Rats Breast Tumor. Res J Pharm Technol. 2020; 13(12): 5811-5815. doi:10.5958/0974-360X.2020.01013.6
12. Akhouri V, Kumari M, Kumar A. Therapeutic effect of Aegle marmelos fruit extract against DMBA induced breast cancer in rats. Sci Rep. 2020; 10(1): 1-12. doi:10.1038/s41598-020-72935-2
13. Lv Z, Guo Y. Metformin and Its Benefits for Various Diseases. Front Endocrinol (Lausanne). 2020; 11(April): 1-10. doi:10.3389/fendo.2020.00191
14. Avijit M, Ashini S. A Review on Metformin: Clinical Significance and Side Effects. Res J Pharm Technol. 2021; 14(11): 6179-6186. doi:10.52711/0974-360X.2021.01070
15. Cejuela M, Martin-Castillo B, Menendez JA, Pernas S. Metformin and Breast Cancer: Where Are We Now? Int J Mol Sci. 2022; 23(5). doi:10.3390/ijms23052705
16. De A, Kuppusamy G. Metformin in breast cancer: preclinical and clinical evidence. Curr Probl Cancer. 2020; 44(1): 100488. doi:10.1016/j.currproblcancer.2019.06.003
17. Babu A, Veerasamy R, Sivadasan S. Metformin- A Drug of Plant Origin. Res J Pharm Technol. 2018; 11(6): 2701-2708. doi:10.5958/0974-360X.2018.00499.7
18. Kamalambigeswari R, Sharmila S, Kowsalya E, Janani SS, Deva V, Rebecca LJ. Extraction of Omega-3 Fatty Acid -methyl stearate from Soil Fungi (Fusarium sp.). Res J Pharm Technol. 2019; 12(9): 4295-4295. doi:10.5958/0974-360X.2019.00738.8
19. Augimeri G, Montalto FI, Giordano C, et al. Nutraceuticals in the mediterranean diet: Potential avenues for breast cancer treatment. Nutrients. 2021; 13(8): 1-24. doi:10.3390/nu13082557
20. Lange KW. Omega-3 fatty acids and mental health. Glob Heal J. 2020; 4(1): 18-30. doi:10.1016/j.glohj.2020.01.004
21. Ito MK. A comparative overview of prescription omega-3 fatty acid products. P T. 2015; 40(12).
22. Liu J, Ma DWL. The role of n-3 polyunsaturated fatty acids in the prevention and treatment of breast cancer. Nutrients. 2014; 6(11): 5184-5223. doi:10.3390/nu6115184
23. Abd-Ellatef GEF, Ahmed OM, Abdel-Reheim ES, Abdel-Hamid AHZ. Ulva lactuca polysaccharides prevent Wistar rat breast carcinogenesis through the augmentation of apoptosis, enhancement of antioxidant defense system, and suppression of inflammation. Breast Cancer Targets Ther. 2017; 9: 67-83. doi:10.2147/BCTT.S125165
24. Checkley LA, Rudolph MC, Wellberg EA, et al. Metformin accumulation correlates with organic cation transporter 2 protein expression and predicts mammary tumor regression in vivo. Cancer Prev Res. 2017; 10(3): 198-207. doi:10.1158/1940-6207.CAPR-16-0211-T
25. Atakisi O, Atakisi E, Ozcan A, Karapehlivan M, Kart A. Protective effect of omega-3 fatty acids on diethylnitrosamine toxicity in rats. Eur Rev Med Pharmacol Sci. 2013; 17(4): 467-471.
26. El-Ashmawy NE, El-Zamarany EA, Khedr NF, Selim HM, Khedr EG. New Shining Stars in The Sky of Breast Cancer Diagnosis and Prognosis: A Review. Res J Pharm Technol. 2022; 15(8): 3808-3813. doi:10.52711/0974-360X.2022.00639
27. Ferreira T, Gama A, Seixas F, et al. Mammary Glands of Women, Female Dogs and Female Rats: Similarities and Differences to Be Considered in Breast Cancer Research. Vet Sci. 2023; 10(6). doi:10.3390/vetsci10060379
28. Fidianingsih I, Aryandono T, Widyarini S, Herwiyanti S. Profile of Histopathological Type and Molecular Subtypes of Mammary Cancer of DMBA-induced Rat and its Relevancy to Human Breast Cancer. Open Access Maced J Med Sci. 2022; 10(A): 71-78. doi:10.3889/oamjms.2022.7975
29. Allred DC. Ductal carcinoma in situ: Terminology, classification, and natural history. J Natl Cancer Inst - Monogr. 2010; (41): 134-138. doi:10.1093/jncimonographs/lgq035
30. Zeweil MM, Sadek KM, Taha NM, El-Sayed Y, Menshawy S. Graviola attenuates DMBA-induced breast cancer possibly through augmenting apoptosis and antioxidant pathway and downregulating estrogen receptors. Environ Sci Pollut Res. 2019; 26(15): 15209-15217. doi:10.1007/s11356-019-04920-w
31. Rahayu IN, Kumala AR, Taruna D, Husodo SD, Dagradi EM, Sukmana J. Improvement of Liver Function (AST and ALT) and Liver Tissue Catalase levels of Wistar rats induced with Alloxan by consuming Catfish oil extract. Res J Pharm Technol. 2024; 17(8): 3676-3684. doi:10.52711/0974-360X.2024.00573
32. Olatosin T, Akinduko D, Uche C. Antioxidant capacity of Moringa oleifera seed oil against CCl4-induced hepatocellular lipid peroxidation in Wistar albino rats. J Exp Biol. 2014; 4(1): 514-518. http://pelagiaresearchlibrary.com/european-journal-of-experimental-biology/vol4-iss1/EJEB-2014-4-1-514-518.pdf
33. Hamza AA, Khasawneh MA, Elwy HM, Hassanin SO, Elhabal SF, Fawzi NM. Salvadora persica attenuates DMBA-induced mammary cancer through downregulation oxidative stress, estrogen receptor expression and proliferation and augmenting apoptosis. Biomed Pharmacother. 2022; 147. doi:10.1016/j.biopha.2022.112666
34. Nassan MA, Aldhahrani A, Amer HH, et al. Investigation of the Anticancer Effect of α-Aminophosphonates and Arylidine Derivatives of 3-Acetyl-1-aminoquinolin-2(1H)-one on the DMBA Model of Breast Cancer in Albino Rats with In Silico Prediction of Their Thymidylate Synthase Inhibitory Effect. Molecules. 2022; 27(3): 1-22. doi:10.3390/molecules27030756
35. Hophan SL, Odnokoz O, Liu H, et al. Ductal Carcinoma In Situ of Breast: From Molecular Etiology to Therapeutic Management. Endocrinol (United States). 2022; 163(4): 1-9. doi:10.1210/endocr/bqac027
36. Wang J, Li B, Luo M, et al. Progression from ductal carcinoma in situ to invasive breast cancer: molecular features and clinical significance. Signal Transduct Target Ther. 2024; 9(1): 1-28. doi:10.1038/s41392-024-01779-3
37. Udumula MP, Poisson LM, Dutta I, et al. Divergent Metabolic Effects of Metformin Merge to Enhance Eicosapentaenoic Acid Metabolism and Inhibit Ovarian Cancer In Vivo. Cancers (Basel). 2022; 14(6). doi:10.3390/cancers14061504
38. Zhang J, Li G, Chen Y, et al. Metformin inhibits tumorigenesis and tumor growth of breast cancer cells by upregulating miR-200c but downregulating AKT2 expression. J Cancer. 2017; 8(10): 1849-1864. doi:10.7150/jca.19858
39. Udumula MP, Dimitrova I, Sakr S, Buekers TE, Giri S, Rattan R. Omega-3 lipid metabolites as mediators of metformin’s anti-proliferative effect in ovarian cancer. Gynecol Oncol. 2020; 159: 124. doi:10.1016/j.ygyno.2020.05.148
40. Udumula MP, Poisson LM, Dutta I, et al. Divergent Metabolic Effects of Metformin Merge to Enhance Eicosapentaenoic Acid Metabolism and Inhibit Ovarian Cancer In Vivo. Cancers (Basel). 2022; 14(6). doi:10.3390/cancers14061504
41. Schexnayder C, Broussard K, Onuaguluchi D, et al. Metformin inhibits migration and invasion by suppressing ROS production and COX2 expression in MDA-MB-231 breast cancer cells. Int J Mol Sci. 2018; 19(11): 1-13. doi:10.3390/ijms19113692
42. Kusmardi K, Adare PD, Kodariah R. The Effect of Omega-3-enriched Fish oil on the Inflammation of Mice Colon Induced by AOM and DSS: Study on COX-2. Res J Pharm Technol. 2019; 12(11): 5265-5268. doi:10.5958/0974-360X.2019.00911.9
43. SS R, S M, BR B, SK D. Protection Against Dimethylbenz[a] Anthracene-Induced Breast Cancer in Female Rats by α-Lactalbumin. Int J Cancer Oncol. 2016; 3(1): 1-6. doi:10.15436/2377-0902.16.026
44. El-Sisi AE, Sokar SS, El-Sayad ME, Moussa EA, Salim EI. Anticancer effect of metformin against 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine-induced rat mammary carcinogenesis is through AMPK pathway and modulation of oxidative stress markers. Hum Exp Toxicol. 2019; 38(6): 703-712. doi:10.1177/0960327119839192
45. Mobasher MA, El-Tantawi HG, El-Said KS. Metformin Ameliorates Oxidative Stress Induced by Diabetes Mellitus and Hepatocellular Carcinoma in Rats. Reports Biochem Mol Biol. 2020; 9(1): 115-128. doi:10.29252/rbmb.9.1.115