Addition of Beetroot Extract to Neoadjuvant Adriamycin Cyclophosphamide Regimen Increased Tumor Cell Apoptosis in Mammary Adenocarcinoma Rats

Sri Susilowati, Neni Susilaningsih, Catharina Suharti

Abstract


Apoptosis is one of the anticancer targets. Currently, the concomitant use of phytotherapy products and chemotherapy regimens is common in breast cancer patients. The purpose of this study was to examine the apoptotic effect of adding beetroot extract to the neoadjuvant Adriamycin Cyclophosphamide (AC) regimen by observing the expression levels of p53 and caspase 3 in tumor tissue from mammary adenocarcinoma rats. Twenty-four rats that succeeded in growing tumor nodules were randomly divided into 4 treatment groups: without treatment, AC only treatment, AC plus beetroot extract at dose of 25 and 100 mg/kg BW, respectively. AC was given 4 cycles in doses of 5 and 50 mg/kg body weight intraperitoneally every week. Tumor tissue was dissected at 4th week for examination of p53 and caspase 3 expression levels using the qRT-PCR method. The addition of beetroot extract at doses of 25 and 100 mg/kg BW in the neoadjuvant AC regimen showed significantly higher levels of p53 and caspase 3 expression than those with AC treatment alone. These results proved that beetroot extract has a synergistic effect with neoadjuvant AC regimen by increasing tumor cells apoptosis.


Keywords: Beetroot extract, Adriamycin, Cyclophosphamide, apoptosis, p53.


Full Text:

PDF

References


Alvarado, A., Lopes, A.C., Faustino-Rocha, A.I., Cabrita, A.M.S., Ferreira, R., Oliveira, P.A., and Colaço, B., 2017, Prognostic factors in MNU and DMBA-induced mammary tumors in female rats, Pathology Research and Practice, 213(5), 441–446. CrossRef

Aubrey, B.J., Kelly, G.L., Janic, A., Herold, M.J., and Strasser, A, 2018, How does p53 induce apoptosis and how does this relate to p53-mediated tumour suppression?, Cell Death and Differentiation, 25(1), 104–113. CrossRef

Boice, A., and Bouchier-Hayes, L., 2020, Targeting apoptotic caspases in cancer, Biochimica et Biophysica Acta-Molecular Cell Research, 1867(6), 118688. CrossRef

D’Arcy, M.S., 2019, Cell death: a review of the major forms of apoptosis, necrosis and autophagy, Cell Biology International, 43(6), 582–592. CrossRef

Drozdoff, L., Klein, E., Kiechle, M., and Paepke, D., 2018, Use of biologically-based complementary medicine in breast and gynecological cancer patients during systemic therapy, BMC Complementary and Alternative Medicine, 18(1), 45–49. CrossRef

Fisusi, F.A., and Akala, E.O., 2019, Drug Combinations in Breast Cancer Therapy, Pharmaceutical Nanotechnology, 7(1), 3–23. CrossRef

Gangadharan, C., Thoh, M., and Manna, S.K., 2009, Inhibition of constitutive activity of nuclear transcription factor kappaB sensitizes doxorubicin-resistant cells to apoptosis, Journal of Cellular Biochemistry, 107(2), 203–213. CrossRef

Gene All Biotechnology, 2016, Ribospin II Protocol Handbook, 314, Seoul, South Korea.

Kapadia, G.J., Azuine, A., Subba Rao, M., Arai, G., Iida, T.A., and Tokuda, H., 2011, Cytotoxic Effect of the Red Beetroot (Beta vulgaris L.) Extract Compared to Doxorubicin (Adriamycin) in the Human Prostate (PC-3) and Breast (MCF-7) Cancer Cell Lines, Anti-Cancer Agents in Medicinal Chemistry, 11(3), 280–284. CrossRef

Kapadia, G.J., Rao, G.S., Ramachandran, C., Iida, A., Suzuki, N., and Tokuda, H., 2013, Synergistic cytotoxicity of red beetroot (Beta vulgaris L.) extract with doxorubicin in human pancreatic, breast and prostate cancer cell lines, Journal of Complementary & Integrative Medicine, 10(1), 113–122. CrossRef

Livak, K.J., and Schmittgen, T.D., 2001, Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCT method, Methods, 25(4), 402–408. CrossRef

Lopes, C.M., Dourado, A., and Oliveira, R., 2017, Phytotherapy and Nutritional Supplements on Breast Cancer, BioMed Research International, 2017. CrossRef

McDonald, E.S., Clark, A.S., Tchou, J., Zhang, P., and Freedman, G.M., 2016, Clinical Diagnosis and Management of Breast Cancer, Journal of Nuclear Medicine, 57(Supplement_1), 9S-16S. CrossRef

Nowacki, L., Vigneron, P., Rotellini, L., Cazzola, H., Merlier, F., Prost, E., Ralanairina, R., Gadonna, J.-P., Rossi, C., and Vayssade, M., 2015, Betanin-enriched red beetroot ({Beta} vulgaris {L}.) extract induces apoptosis and autophagic cell death in {MCF}-7 cells, Phytother. Res., 1973(April), 1964–1973. CrossRef

Ogino M.H. and Tadi, P., 2021, Cyclophosphamide, Treasure Island (FL), StatPearls Publishing. Available from: https://www.ncbi.nlm.nih.gov/books/NBK553087/

Pu, X., Storr, S.J., Zhang, Y., Rakha, E.A., Green, A.R., Ellis, I.O., and Martin, S.G., 2017, Caspase-3 and caspase-8 expression in breast cancer: caspase-3 is associated with survival, Apoptosis, 22(3), 357–368. CrossRef

Sharma, P., 2014, Identification and validation of an anthracycline/cyclophosphamide-based chemotherapy response assay in breast cancer, Breast Diseases, 25(3), 235–237. CrossRef

Siddik, Z., 2002, Mechanisms of action of cancer chemotherapeutic agents: DNA-interactive alkylating agents and antitumour platinum-based drugs, Cancer Journal, 78, 156–162. CrossRef

Tacar, O., Sriamornsak, P., and Dass, C.R., 2013, Doxorubicin: An update on anticancer molecular action, toxicity and novel drug delivery system, Journal of Pharmacy and Pharmacology, 65(2), 157–170. CrossRef




DOI: http://dx.doi.org/10.14499/indonesianjcanchemoprev12iss3pp130-136

Copyright (c) 2022 Sri Susilowati

Indexed by:

               

               

      

 

Indonesian Society for Cancer Chemoprevention