Research Article
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Evaluation of Tumor-Suppressive Properties and Apoptotic Functions of Mad Honey and Vincristine Applications in a Rat Model of Breast Cancer

Year 2024, Accepted Papers, 1 - 13

Efe Kurtdede Mehmet Eray Alçığır Ahmet Mahmut Alperen Berk Baran Necat Kuzu Erman Gülendağ

https://doi.org/10.33988/auvfd.1281608

Abstract

Bu çalışmada, sıçanlarda 7,12-dimetilbenz[a]antrasen (DMBA) ile indüklenen bir meme tümörü modelinde vinkristin ve deli balın tek başına ve birlikte uygulanmasındaki baskılayıcı etkileri biyokimyasal, hematolojik ve histopatolojik olarak araştırıldı. 43-49 günlük toplam 72 rat 12 rattan oluşan 6 gruba ayrıldı.
Kontrol grubu (CG) sağlıklı sıçanlardan oluştu. Araç grubu (VG) sadece araç maddesi aldı ve kanser kontrol grubu (CCG) sadece DMBA aldı. Bal grubuna (HG) sadece Türk deli balı verildi. Vinkristin grubu (VinG) sadece vinkristin ve vinkristin-bal grubu (VHG) hem Türk deli balı hem de vinkristin aldı. 13 haftalık deneme süresinin son 4 haftasında Türk deli balı ve/veya vinkristin verildi.
Lökosit ve lenfosit sayıları CCG ve VG gruplarında anlamlı farklılık gösterdi. Alanin transaminaz ve total protein seviyeleri CCG ve VinG gruplarında daha yüksekti. Aspartat transaminaz CCG, HG ve VG gruplarında daha yüksekti. Kreatinin diğer tüm gruplarda HG grubundaki değere göre daha yüksekti. Kaspaz-3 ve Bax protein seviyeleri CG ve VG gruplarında daha yüksek, kaspaz-8 ve -9 ise daha düşüktü. Bax-xL, CCG grubunda daha fazla arttı. HG ve VinG gruplarında anaplazi azaldı, ancak apoptoz ve diğer hücresel hasarlar arttı.
Bu DMBA kaynaklı meme kanseri modelinde deli bal ve vincristine'in birlikte etkili terapötik ajanlar olarak kabul edilebileceği sonucuna varıldı.

Keywords

Breast Cancer Rat Apoptosis Turkish Mad Honey

Supporting Institution

This study was supported by Ankara University Scientific Research.

Project Number

21B0239002.

Thanks

We would like to thank Ankara University Scientific Research Institution for their support.

References

  • Alzahrani HA, Boukraa L, Bellik Y, et al (2012): Evaluation of the Antioxidant Activity of Three Varieties of Honey from Different Botanical and Geographical Origins. Glob J Health Sci, 4, 192-196.
  • Bargou RC, Wagener C, Bommert K, et al (1996): Overexpression of the death-promoting gene bax-alpha which is downregulated in breast cancer restores sensitivity to different apoptotic stimuli and reduces tumor growth in SCID mice. J Clin Invest, 97, 2651-2659.
  • Beaudu-Lange C, Larrat S, Lange E, et al (2021): Prevalence of Reproductive Disorders including Mammary Tumors and Associated Mortality in Female Dogs. Vet Sci, 8, 184.
  • Blanc C, Deveraux QL, Krajewski S, et al (2000): Caspase-3 is essential for procaspase-9 processing and cisplatin-induced apoptosis of MCF-7 breast cancer cells. Cancer Res, 60, 4386-4390.
  • Blazquez S, Sirvent JJ, Olona M, et al (2006): Caspase-3 and caspase-6 in ductal breast carcinoma: a descriptive study. Histol Histopathol, 21, 1321-1329.
  • Buratti S, Benedetti S, Cosio MS (2007): Evaluation of the antioxidant power of honey, propolis and royal jelly by amperometric flow injection analysis. Talanta. 71, 1387-1392.
  • Cavalcanti C, Costa-Lotufo LV, Moraes MO, et al (2006): Genotoxicity evaluation of kaurenoic acid, a bioactive diterpenoid present in Copaiba oil. Food Chem Toxicol, 44, 338-392.
  • Chen J, Li S, Shen Q, et al (2011): Enhanced cellular uptake of folic acid-conjugated PLGA-PEG nanoparticles loaded with vincristine sulfate in human breast cancer. Drug Dev Ind Pharm, 37, 1339–1346.
  • Chipuk JE, Moldoveanu T, Llambi F, et al (2010): The BCL-2 family reunion. Mol Cell, 37, 299-310.
  • Christou M, Savas U, Schroeder S, et al (1995) Cytochromes CYP1a1 and CYP1B1 in the rat mammary gland: cell specific expression and regulation by polycyclic aromatic hydrocarbons and hormones. Mol Cell Endocrinol, 115, 41-50.
  • Danial NN, Korsmeyer SJ (2004): Cell death: critical control points. Cell, 116, 205-219.
  • Farombi EO, Shrotriya S, Surh YJ (2009): Kolaviron inhibits dimethyl nitrosamine-induced liver injury by suppressing COX-2 and iNOS expression via NF-ÍB and AP-1. Life Sci, 84,149-155.
  • Goldschmidt M, Pena L, Rasotto R, et al (2011): Classification and grading of canine mammary tumors. Vet Pathol, 48, 117-131.
  • Guillen KP, Fujita M, Butterfield AJ, et al (2022): A human breast cancer-derived xenograft and organoid platform for drug discovery and precision oncology. Nat Cancer, 3, 232–250.
  • Gulbahce ME, Baltaci S, Oztekin M, et al (2021): The Effect of Zinc and Melatonin Administration on Lipid Peroxidation, IL-6 Levels, and Element Metabolism in DMBA-Induced Breast Cancer in Rats. Biol Trace Elem Res, 199.
  • Holen I, Speirs V, Morrissey B, et al (2017): In vivo models in breast cancer research: progress, challenges and future directions. Dis Models Mech, 10, 359-371.
  • Jansen SA, Kleerekooper I, Hofman ZL, et al (2012): Grayanotoxin poisoning: ‘mad honey disease’ and beyond. Cardiovasc Toxicol, 12, 208-215.
  • Kabel AM (2017): Tumor markers of breast cancer: New prospectives. J Oncol Sci, 3, 5-11.
  • Kayaselcuk F, Nursal TZ, Polat A, et al (2004): Expression of survivin, bcl-2, P53 and bax in breast carcinoma and ductal intraepithelial neoplasia (DIN 1a). J Exp Clin Cancer Res, 23, 105-112.
  • Kennedy SM, O’Driscoll L, Purcell R, et al (2003) Prognostic importance of survivin in breast cancer. Br J Cancer, 88, 1077-1083.
  • LaCasse EC, Baird S, Korneluk RG, et al (1998): The inhibitors of apoptosis (IAPs) and their emerging role in cancer. Oncogene, 17, 3247-3259.
  • Luna LG (1968): Manual of Histologic Staining Methods; Armed Forces Institute of Pathology (U.S.); Editor, Lee G. Luna; Edition, 3; Publisher, McGraw-Hill, 1968.
  • Mohamed AM, Abdalla MS, Rizk MZ, et al (2014): Alleviation of Dimethylnitrosamine-induced liver injury and fibrosis by supplementation of Anabasis articulata extract in rats. Indian J Clin Biochem, 29, 418-429.
  • Moulder S, Hortobagyi GN (2008): Advances in the treatment of breast cancer. Clin Pharmacol Ther, 83, 26-36.
  • Nandakumar N, Balasubramanian MP (2011): Hesperidin protects renal and hepatic tissues against free radical-mediated oxidative stress during DMBA-induced experimental breast cancer. J Environ Pathol Toxicol Oncol, 30, 283-300.
  • Narimane S, Demircan E, Akkal S, et al (2017): Correlation between antioxidant activity and phenolic acids profile and content of Algerian propolis: Influence of solvent. Pak J Pharm Sci, 30, 1417-1423.
  • Oh JW, Yang WI, Lee MJ, et al (2009): The prognostic significance of survivin expression in breast cancer. J Breast Cancer, 12, 285-294.
  • Ohkawa H, Ohishi N, Yagi K (1979): Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem, 195, 351-358.
  • Okada E, Murai Y, Matsui K, et al (2001): Survivin expression in tumor cell nuclei is predictive of a favorable prognosis in gastric cancer patients. Cancer Lett, 163, 109-116.
  • Ozdemir H, Oto G, Ekin S, et al (2017): The protective effects of Lepidium sativum l. In 7,12-dimethylbenz(a)anthracene applied rats. Fresenius Environ Bull, 26, 2446-2453.
  • Pakkiri P, Lakhani SR, Smart CE (2009): Current and future approach to the pathologist’s assessment for targeted therapy in breast cancer. Pathology, 4189-4199.
  • Pu X, Storr SJ, Zhang Y, et al (2017): Caspase-3 and caspase-8 expression in breast cancer: caspase-3 is associated with survival. Apoptosis, 22, 357-368.
  • Russo J, Russo IH (2000): Atlas and histologic classification of tumors of the rat mammary gland. J Mammary Gland Biol Neoplasia, 5, 187-200.
  • Ryan BM, Konecny GE, Kahlert S, et al (2006): Survivin expression in breast cancer predicts clinical outcome and is associated with HER2, VEGF, urokinase plasminogen activator and PAI-1. Ann Oncol, 17, 597-604.
  • Sahin A, Türkmen S, Güzel N, et al (2018): A Comparison of the Effects of GrayanotoxinContaining Honey (Mad Honey), Normal Honey, and Propolis on Fracture Healing. Med Princ Pract, 27, 99-106.
  • Sharifi S, Barar J, Hejazi MS, et al (2014): Roles of the Bcl-2/Bax ratio, caspase-8 and 9 in resistance of breast cancer cells to paclitaxel. Asian Pac J Cancer Prev, 15, 8617-8622.
  • Sheikh A, Hussain SA, Ghori Q, et al (2015): The spectrum of genetic mutations in breast cancer. Asian Pac J Cancer Prev, 16, 2177-2185.
  • Shi Y (2002): Mechanisms of caspase activation and inhibition during apoptosis. Mol Cell, 9, 459-470.
  • Shokouh TZ, Ezatollah A, Barand P (2015): Interrelationships Between Ki67, HER2/neu, p53, ER, and PR Status and Their Associations With Tumor Grade and Lymph Node Involvement in Breast Carcinoma Subtypes: Retrospective-Observational Analytical Study. Medicine (Baltimore), 94, 1359.
  • Sun Y, Oberley LW, Li Y (1988): A simple method for clinical assay of superoxide dismutase. Clin Chem, 34, 497-500.
  • Tanaka K, Iwamoto S, Gon G, et al (2000): Expression of survivin and its relationship to loss of apoptosis in breast carcinomas. Clin Cancer Res, 6, 127-134.
  • Testa U, Castelli G, Pelosi E (2020): Breast Cancer: A Molecularly Heterogenous Disease Needing Subtype-Specific Treatments. Med Sci (Basel), 8, 18.
  • Thomas E, Holmes FA, Smith TL, et al (2004): The use of alternate, non-cross-resistant adjuvant chemotherapy on the basis of pathologic response to a neoadjuvant doxorubicin-based regimen in women with operable breast cancer: long-term results from a prospective randomized trial. J Clin Oncol, 22, 2294-2302.
  • Wolf EJ, Harrington KM, Clark SL, et al (2013): Sample Size Requirements for Structural Equation Models: An Evaluation of Power, Bias, and Solution Propriety. Educational and Psychological Measurement, 6, 913–934.

Year 2024, Accepted Papers, 1 - 13

Efe Kurtdede Mehmet Eray Alçığır Ahmet Mahmut Alperen Berk Baran Necat Kuzu Erman Gülendağ

https://doi.org/10.33988/auvfd.1281608

Abstract

Project Number

21B0239002.

References

  • Alzahrani HA, Boukraa L, Bellik Y, et al (2012): Evaluation of the Antioxidant Activity of Three Varieties of Honey from Different Botanical and Geographical Origins. Glob J Health Sci, 4, 192-196.
  • Bargou RC, Wagener C, Bommert K, et al (1996): Overexpression of the death-promoting gene bax-alpha which is downregulated in breast cancer restores sensitivity to different apoptotic stimuli and reduces tumor growth in SCID mice. J Clin Invest, 97, 2651-2659.
  • Beaudu-Lange C, Larrat S, Lange E, et al (2021): Prevalence of Reproductive Disorders including Mammary Tumors and Associated Mortality in Female Dogs. Vet Sci, 8, 184.
  • Blanc C, Deveraux QL, Krajewski S, et al (2000): Caspase-3 is essential for procaspase-9 processing and cisplatin-induced apoptosis of MCF-7 breast cancer cells. Cancer Res, 60, 4386-4390.
  • Blazquez S, Sirvent JJ, Olona M, et al (2006): Caspase-3 and caspase-6 in ductal breast carcinoma: a descriptive study. Histol Histopathol, 21, 1321-1329.
  • Buratti S, Benedetti S, Cosio MS (2007): Evaluation of the antioxidant power of honey, propolis and royal jelly by amperometric flow injection analysis. Talanta. 71, 1387-1392.
  • Cavalcanti C, Costa-Lotufo LV, Moraes MO, et al (2006): Genotoxicity evaluation of kaurenoic acid, a bioactive diterpenoid present in Copaiba oil. Food Chem Toxicol, 44, 338-392.
  • Chen J, Li S, Shen Q, et al (2011): Enhanced cellular uptake of folic acid-conjugated PLGA-PEG nanoparticles loaded with vincristine sulfate in human breast cancer. Drug Dev Ind Pharm, 37, 1339–1346.
  • Chipuk JE, Moldoveanu T, Llambi F, et al (2010): The BCL-2 family reunion. Mol Cell, 37, 299-310.
  • Christou M, Savas U, Schroeder S, et al (1995) Cytochromes CYP1a1 and CYP1B1 in the rat mammary gland: cell specific expression and regulation by polycyclic aromatic hydrocarbons and hormones. Mol Cell Endocrinol, 115, 41-50.
  • Danial NN, Korsmeyer SJ (2004): Cell death: critical control points. Cell, 116, 205-219.
  • Farombi EO, Shrotriya S, Surh YJ (2009): Kolaviron inhibits dimethyl nitrosamine-induced liver injury by suppressing COX-2 and iNOS expression via NF-ÍB and AP-1. Life Sci, 84,149-155.
  • Goldschmidt M, Pena L, Rasotto R, et al (2011): Classification and grading of canine mammary tumors. Vet Pathol, 48, 117-131.
  • Guillen KP, Fujita M, Butterfield AJ, et al (2022): A human breast cancer-derived xenograft and organoid platform for drug discovery and precision oncology. Nat Cancer, 3, 232–250.
  • Gulbahce ME, Baltaci S, Oztekin M, et al (2021): The Effect of Zinc and Melatonin Administration on Lipid Peroxidation, IL-6 Levels, and Element Metabolism in DMBA-Induced Breast Cancer in Rats. Biol Trace Elem Res, 199.
  • Holen I, Speirs V, Morrissey B, et al (2017): In vivo models in breast cancer research: progress, challenges and future directions. Dis Models Mech, 10, 359-371.
  • Jansen SA, Kleerekooper I, Hofman ZL, et al (2012): Grayanotoxin poisoning: ‘mad honey disease’ and beyond. Cardiovasc Toxicol, 12, 208-215.
  • Kabel AM (2017): Tumor markers of breast cancer: New prospectives. J Oncol Sci, 3, 5-11.
  • Kayaselcuk F, Nursal TZ, Polat A, et al (2004): Expression of survivin, bcl-2, P53 and bax in breast carcinoma and ductal intraepithelial neoplasia (DIN 1a). J Exp Clin Cancer Res, 23, 105-112.
  • Kennedy SM, O’Driscoll L, Purcell R, et al (2003) Prognostic importance of survivin in breast cancer. Br J Cancer, 88, 1077-1083.
  • LaCasse EC, Baird S, Korneluk RG, et al (1998): The inhibitors of apoptosis (IAPs) and their emerging role in cancer. Oncogene, 17, 3247-3259.
  • Luna LG (1968): Manual of Histologic Staining Methods; Armed Forces Institute of Pathology (U.S.); Editor, Lee G. Luna; Edition, 3; Publisher, McGraw-Hill, 1968.
  • Mohamed AM, Abdalla MS, Rizk MZ, et al (2014): Alleviation of Dimethylnitrosamine-induced liver injury and fibrosis by supplementation of Anabasis articulata extract in rats. Indian J Clin Biochem, 29, 418-429.
  • Moulder S, Hortobagyi GN (2008): Advances in the treatment of breast cancer. Clin Pharmacol Ther, 83, 26-36.
  • Nandakumar N, Balasubramanian MP (2011): Hesperidin protects renal and hepatic tissues against free radical-mediated oxidative stress during DMBA-induced experimental breast cancer. J Environ Pathol Toxicol Oncol, 30, 283-300.
  • Narimane S, Demircan E, Akkal S, et al (2017): Correlation between antioxidant activity and phenolic acids profile and content of Algerian propolis: Influence of solvent. Pak J Pharm Sci, 30, 1417-1423.
  • Oh JW, Yang WI, Lee MJ, et al (2009): The prognostic significance of survivin expression in breast cancer. J Breast Cancer, 12, 285-294.
  • Ohkawa H, Ohishi N, Yagi K (1979): Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem, 195, 351-358.
  • Okada E, Murai Y, Matsui K, et al (2001): Survivin expression in tumor cell nuclei is predictive of a favorable prognosis in gastric cancer patients. Cancer Lett, 163, 109-116.
  • Ozdemir H, Oto G, Ekin S, et al (2017): The protective effects of Lepidium sativum l. In 7,12-dimethylbenz(a)anthracene applied rats. Fresenius Environ Bull, 26, 2446-2453.
  • Pakkiri P, Lakhani SR, Smart CE (2009): Current and future approach to the pathologist’s assessment for targeted therapy in breast cancer. Pathology, 4189-4199.
  • Pu X, Storr SJ, Zhang Y, et al (2017): Caspase-3 and caspase-8 expression in breast cancer: caspase-3 is associated with survival. Apoptosis, 22, 357-368.
  • Russo J, Russo IH (2000): Atlas and histologic classification of tumors of the rat mammary gland. J Mammary Gland Biol Neoplasia, 5, 187-200.
  • Ryan BM, Konecny GE, Kahlert S, et al (2006): Survivin expression in breast cancer predicts clinical outcome and is associated with HER2, VEGF, urokinase plasminogen activator and PAI-1. Ann Oncol, 17, 597-604.
  • Sahin A, Türkmen S, Güzel N, et al (2018): A Comparison of the Effects of GrayanotoxinContaining Honey (Mad Honey), Normal Honey, and Propolis on Fracture Healing. Med Princ Pract, 27, 99-106.
  • Sharifi S, Barar J, Hejazi MS, et al (2014): Roles of the Bcl-2/Bax ratio, caspase-8 and 9 in resistance of breast cancer cells to paclitaxel. Asian Pac J Cancer Prev, 15, 8617-8622.
  • Sheikh A, Hussain SA, Ghori Q, et al (2015): The spectrum of genetic mutations in breast cancer. Asian Pac J Cancer Prev, 16, 2177-2185.
  • Shi Y (2002): Mechanisms of caspase activation and inhibition during apoptosis. Mol Cell, 9, 459-470.
  • Shokouh TZ, Ezatollah A, Barand P (2015): Interrelationships Between Ki67, HER2/neu, p53, ER, and PR Status and Their Associations With Tumor Grade and Lymph Node Involvement in Breast Carcinoma Subtypes: Retrospective-Observational Analytical Study. Medicine (Baltimore), 94, 1359.
  • Sun Y, Oberley LW, Li Y (1988): A simple method for clinical assay of superoxide dismutase. Clin Chem, 34, 497-500.
  • Tanaka K, Iwamoto S, Gon G, et al (2000): Expression of survivin and its relationship to loss of apoptosis in breast carcinomas. Clin Cancer Res, 6, 127-134.
  • Testa U, Castelli G, Pelosi E (2020): Breast Cancer: A Molecularly Heterogenous Disease Needing Subtype-Specific Treatments. Med Sci (Basel), 8, 18.
  • Thomas E, Holmes FA, Smith TL, et al (2004): The use of alternate, non-cross-resistant adjuvant chemotherapy on the basis of pathologic response to a neoadjuvant doxorubicin-based regimen in women with operable breast cancer: long-term results from a prospective randomized trial. J Clin Oncol, 22, 2294-2302.
  • Wolf EJ, Harrington KM, Clark SL, et al (2013): Sample Size Requirements for Structural Equation Models: An Evaluation of Power, Bias, and Solution Propriety. Educational and Psychological Measurement, 6, 913–934.
There are 44 citations in total.

Details

Primary Language English
Subjects Veterinary Surgery
Journal Section Research Article
Authors

Efe Kurtdede 0000-0001-8436-3332

Mehmet Eray Alçığır 0000-0002-5165-5854

Ahmet Mahmut Alperen 0000-0002-4871-4841

Berk Baran 0000-0002-0461-8006

Necat Kuzu 0009-0005-5831-2642

Erman Gülendağ 0000-0002-3335-7247

Project Number 21B0239002.
Early Pub Date October 27, 2023
Publication Date
Published in Issue Year 2024Accepted Papers

Cite

APA Kurtdede, E., Alçığır, M. E., Alperen, A. M., Baran, B., et al. (2023). Evaluation of Tumor-Suppressive Properties and Apoptotic Functions of Mad Honey and Vincristine Applications in a Rat Model of Breast Cancer. Ankara Üniversitesi Veteriner Fakültesi Dergisi1-13. https://doi.org/10.33988/auvfd.1281608
AMA Kurtdede E, Alçığır ME, Alperen AM, Baran B, Kuzu N, Gülendağ E. Evaluation of Tumor-Suppressive Properties and Apoptotic Functions of Mad Honey and Vincristine Applications in a Rat Model of Breast Cancer. Ankara Univ Vet Fak Derg. Published online October 1, 2023:1-13. doi:10.33988/auvfd.1281608
Chicago Kurtdede, Efe, Mehmet Eray Alçığır, Ahmet Mahmut Alperen, Berk Baran, Necat Kuzu, and Erman Gülendağ. “Evaluation of Tumor-Suppressive Properties and Apoptotic Functions of Mad Honey and Vincristine Applications in a Rat Model of Breast Cancer”. Ankara Üniversitesi Veteriner Fakültesi Dergisi, October (October 2023), 1-13. https://doi.org/10.33988/auvfd.1281608.
EndNote Kurtdede E, Alçığır ME, Alperen AM, Baran B, Kuzu N, Gülendağ E (October 1, 2023) Evaluation of Tumor-Suppressive Properties and Apoptotic Functions of Mad Honey and Vincristine Applications in a Rat Model of Breast Cancer. Ankara Üniversitesi Veteriner Fakültesi Dergisi 1–13.
IEEE E. Kurtdede, M. E. Alçığır, A. M. Alperen, B. Baran, N. Kuzu, and E. Gülendağ, “Evaluation of Tumor-Suppressive Properties and Apoptotic Functions of Mad Honey and Vincristine Applications in a Rat Model of Breast Cancer”, Ankara Univ Vet Fak Derg, pp. 1–13, October 2023, doi: 10.33988/auvfd.1281608.
ISNAD Kurtdede, Efe et al. “Evaluation of Tumor-Suppressive Properties and Apoptotic Functions of Mad Honey and Vincristine Applications in a Rat Model of Breast Cancer”. Ankara Üniversitesi Veteriner Fakültesi Dergisi. October 2023. 1-13. https://doi.org/10.33988/auvfd.1281608.
JAMA Kurtdede E, Alçığır ME, Alperen AM, Baran B, Kuzu N, Gülendağ E. Evaluation of Tumor-Suppressive Properties and Apoptotic Functions of Mad Honey and Vincristine Applications in a Rat Model of Breast Cancer. Ankara Univ Vet Fak Derg. 2023;:1–13.
MLA Kurtdede, Efe et al. “Evaluation of Tumor-Suppressive Properties and Apoptotic Functions of Mad Honey and Vincristine Applications in a Rat Model of Breast Cancer”. Ankara Üniversitesi Veteriner Fakültesi Dergisi, 2023, pp. 1-13, doi:10.33988/auvfd.1281608.
Vancouver Kurtdede E, Alçığır ME, Alperen AM, Baran B, Kuzu N, Gülendağ E. Evaluation of Tumor-Suppressive Properties and Apoptotic Functions of Mad Honey and Vincristine Applications in a Rat Model of Breast Cancer. Ankara Univ Vet Fak Derg. 2023:1-13.