Effects of Stryphnodendron adstringens extracts on murine 4T1 tumor line





Carcinoma, Cell Culture, Cerrado Plants, Cytotoxicity, Stryphnodendron adstringens.


Breast cancer appears as the main gynecological cancer and presents high morbidity and mortality. Because most diagnoses are made belatedly, it is necessary to seek therapeutic options that aim for advanced stages of the disease. This study aims to evaluate the antitumoral action of Stryphnodendron adstringens fruit extracts on 4T1 murine mammary carcinoma cell culture. The inhibitory potential of S. adstringens fruit extract on the metalloproteinases (MMPs) 2 and 9 was evaluated through zymography. From these results, MTT assays were performed to evaluate the extracts’ effects on the murine mammary carcinoma 4T1 line cell viability. From the crude extract, the following extracts were obtained: hydroalcoholic (SAFCEA), hexane (SAFCEB), chloroform (SAFCEC), and ethyl acetate (SAFCED). Lastly, the migration of the cells treated with extracts SAFCEA and SAFCED was verified. The hydroalcoholic extract (SAFCEA) was the most efficient in inhibiting gelatinases. During the phytochemical study, it was noted that alkaloids were present in all partitions. The 50 % growth inhibition (IC50) concentrations found were: 40.1 μg/mL (SAFCEA) and 70.14 μg/mL (SAFCED). After the cellular cytotoxicity assay, cell morphology was altered by treatment with the selected partitions (SAFCEA and SAFCED), obtaining morphology consistent with apoptosis. The results demonstrate that S. adstringens extracts exhibit the inhibitory activity of MMP-2 and MMP-9 as well as cytotoxicity toward 4T1 tumor cells. These findings indicate that follow-up studies of the partitions from S. adstringens may lead to the development of novel chemotherapeutics for oncological treatments.


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ALAMZADEH, Z., et al. Ultrastructural and optical characteristics of cancer cells treated by a nanotechnology-based chemo-photothermal therapy method. Journal of Photochemistry & Photobiology, B, Biology. 2019, 192(1), 19-25. https://doi.org/10.1016/j.jphotobiol.2019.01.005

ALIPANAH, H., BIGDELI, M.R. and ESMAEILI, M.A. Inhibitory Effect of Viola odorata Extract on Tumor Growth and Metastasis in 4T1 Breast Cancer Model. Iranian journal of pharmaceutical research: IJPR. 2018, 17(1), 276-291. https://dx.doi.org/10.22037/ijpr.2018.2149

BARBOSA-FILHO, J.M., et al. Anti-inflammatory activity of alkaloids: a twenty-century review. Revista Brasileira de Farmacognosia. 2006, 16(1), 109-134. https://doi.org/10.1590/S0102-695X2006000100020

CARVALHO, J.T.G., et al. Medicinal Plants from Brazilian Cerrado: Antioxidant and Anticancer Potential and Protection against Chemotherapy Toxicity. Oxidative Medicine and Cellular Longevity. 2019, 2019(1), 1-16. https://doi.org/10.1155/2019/3685264

CATHCART, J., PULKOSKI-GROSS, A. and CAO, J., Targeting matrix metalloproteinases in cancer: bringing new life to old ideas. Genes & diseases. 2015, 2(1), 26-34. https://doi.org/10.1016/j.gendis.2014.12.002

CECILIO, A.P., et al. Breast cancer in Brazil: epidemiology and treatment challenges. Breast Cancer: Targets and Therapy. 2015, 7(1), 43-49. https://doi.org/10.2147/BCTT.S50361

CHAN, L.P., et al. IL-8 promotes inflammatory mediators and stimulates activation of p38 MAPK/ERK-NF-κB pathway and reduction of JNK in HNSCC. Oncotarget. 2017, 8(34), 56375-56388. https://doi.org/10.18632/oncotarget.16914

COELHO, J.M., et al. O efeito da Sulfadiazina de prata, extrato de Ipê-roxo e extrato de Barbatimão na cicatrização de feridas cutâneas, em ratos. Revista do Colégio Brasileiro de Cirurgia. 2010, 37(1), 45-51. http://dx.doi.org/10.1590/S0100-69912010000100010

COSTA, M.A., et al. Acute and Chronic Toxicity of an Aqueous Fraction of the Stem Bark of Stryphnodendron adstringens (Barbatimão) in Rodents. Evidence-Based Complementary and Alternative Medicine. 2013, 2013(1), 1-9. https://doi.org/10.1155/2013/841580

MESQUITA, M.L., et al. Cytotoxic activity of Brazilian Cerrado plants used in traditional medicine against cancer cell lines. Journal of ethnopharmacology. 2009, 123(3), 439-445. https://doi.org/10.1016/j.jep.2009.03.018

ELIAS, S.T., et al. Radiation induced a supra-additive cytotoxic effect in head and neck carcinoma cell lines when combined with plant extracts from Brazilian Cerrado biome. Clinical Oral Investigations. 2015, 19(3), 637-646. https://doi.org/10.1007/s00784-014-1289-z

GALI-MUHTASIB, H., et al. Cell death mechanisms of plant-derived anticancer drugs: beyond apoptosis. Apoptosis. 2015, 20(12), 1531-1562. https://doi.org/10.1007/s10495-015-1169-2

HANAHAN, D. and WEINBERG, R.A. Hallmarks of Cancer: The Next Generation. Cell. 2011, 144(5), 646-674. https://doi.org/10.1016/j.cell.2011.02.013

HEPPNER, G.H., MILLER, F.R. and SHEKHAR, P.M. Nontransgenic models of breast cancer. Breast Cancer Research. 2000, 2(5), 331-334. https://doi.org/10.1186/bcr77

HUANG, W.Y., CAI, Y.Z. and ZHANG, Y. Natural phenolic compounds from medicinal herbs and dietary plants: potential use for cancer prevention. Nutrition and cancer. 2009, 62(1), 1-20. https://doi.org/10.1080/01635580903191585

HUGHES, V.S. and SIEMANN, D.W. Treatment with Src inhibitor Dasatinib results in elevated metastatic potential in the 4T1 murine mammary carcinoma model. Tumor & microenvironment. 2018, 1(1), 30-36. https://doi.org/10.4103/tme.tme_19_17

IQBAL, J., et al. Potential phytocompounds for developing breast cancer therapeutics: Nature’s healing touch. European journal of pharmacology. 2018, 827(15), 125-148. https://doi.org/10.1016/j.ejphar.2018.03.007

KOCZURKIEWICZ, P., et al. Multidirectional effects of triterpene saponins on cancer cells - mini-review of in vitro studies. Acta biochimica Polonica. 2014, 62(3), 383-393. https://doi.org/10.18388/abp.2015_1089

KOZŁOWSKI, J., KOZŁOWSKA A. and KOCKI, J. Breast cancer metastasis - insight into selected molecular mechanisms of the phenomenon. Postepy higieny i medycyny doswiadczalnej (Online). 2015, 69(1), 447-451. https://doi.org/10.5604/17322693.1148710

LIN, C.Y., et al. Inhibition of the invasion and migration of renal carcinoma 786‑o‑si3 cells in vitro and in vivo by Koelreuteria formosana extract. Molecular Medicine Reports. 2014, 10(6), 3334-3342. https://doi.org/10.3892/mmr.2014.2587

LIN, H., et al. Iron (II)−polypyridyl complexes inhibit the growth of glioblastoma tumor and enhance TRAIL-induced cell apoptosis. Chemistry an Asian Journal. 2018, 13(18), 2730–2738. https://doi.org/10.1002/asia.201800862

LU, P., WEAVER, V.M. and WERB, Z. The extracellular matrix: A dynamic niche in cancer progression. The Journal of Cell Biology. 2012, 196(4), 395-406. https://doi.org/10.1083/jcb.201102147

LUIZ, R.L.F., et al. Proanthocyanidins polymeric tannin from Stryphnodendron adstringens are active against Candida albicans biofilms. BMC Complementary and Alternative Medicine. 2015, 15(68), 1-11. https://doi.org/10.1186/s12906-015-0597-4

LUO, K.W., et al. In vivo and in vitro anti-tumor and anti-metastasis effects of Coriolus versicolor aqueous extract on mouse mammary 4T1 carcinoma. Phytomedicine. 2014, 21(8-9), 1078-1087. https://doi.org/10.7150/thno.23209

LV, Y., et al. Targeting intracellular MMPs efficiently inhibits tumor metastasis and angiogenesis. Theranostics. 2018, 8(10), 2830-2845. https://doi.org/10.7150/thno.23209

MATOS, F.J.A. Introdução a fitoquímica experimental. 3th ed. Fortaleza: Edições UFC, 2009.

NHO, K.J., CHUN, J.M., KIM, D.S. and KIM, H.K. Ampelopsis japonica ethanol extract suppresses migration and invasion in human MDA‑MB‑231 breast cancer cells. Molecular medicine reports. 2015, 11(5), 3722- 3728. https://doi.org/10.3892/mmr.2015.3179

ONG, M.S., et al. Cytoskeletal Proteins in Cancer and Intracellular Stress: A Therapeutic Perspective. Cancer (Basel). 2020, 12(1), 238. https://doi.org/10.3390/cancers12010238

NETO, J.A.R., et al. Using the plants of Brazilian Cerrado for wound healing: From traditional use to scientific approach. Journal of Ethnopharmacology. 2020, 1(1), 112547. https://doi.org/10.1016/j.jep.2020.112547

RIBEIRO, R.I.M.A., et al. Inibição de metaloproteinases por extratos aquosos de Aloe vera, Annona muricata e chá preto. Bioscience Journal. 2010, 26(1), 121-127.

RUNDHAUG, J.E. Matrix metalloproteinases and angiogenesis. Journal of Cellular and Molecular Medicine. 2005, 9(2), 267-285. https://doi.org/10.1111/j.1582-4934.2005.tb00355.x

SANTOS, K.M., NUNES, D.A.F., GOMES, I.N.F. and RIBEIRO, R.I.M.A. Inhibition of gelatinase activity of MMP-2 and MMP-9 by extracts of Bauhinia ungulata L. Bioscience Journal. 2015, 31(2), 584-590. https://doi.org/10.14393/BJ-v31n2a2015-23477

SANTOS, K.M., et al. ID7 Isolated from Bauhinia variegata Stem Inhibits Tumor Progression and Metastatic Mechanisms of Triple Negative Breast Cancer in Vivo: ID7 fraction from Bauhinia variegata Inhibits Triple Negative Breast Cancer. Journal of Pharmacy and Pharmacology. 2019, 7(1), 368-384. https://doi.org/10.17265/2328-2150/2019.07.003

SLEEMAN, J.P., et al. Concepts of metastasis in flux: the stromal progression model. Seminars in Cancer Biology. 2012, 22(3), 174-186. https://doi.org/10.1016/j.semcancer.2012.02.007

SORENSON, C.M., BARRY, M.A. and EASTMAN, A. Analysis of events associated with cell cycle arrest at G2 phase and cell death induced by cisplatin. Journal of the National Cancer Institute. 1990, 82(9), 749-755. https://doi.org/10.1093/jnci/82.9.749

SOUZA-MOREIRA, T.M., FERNANDES, G.M.Q. and PIETRO, R.C. Stryphnodendron Species Known as “Barbatimão”: A Comprehensive Report. Molecules. 2018, 23(4), 910-935. https://doi.org/10.3390/molecules23040910

WANG, Z., et al. Paeoniflorin inhibits migration and invasion of human glioblastoma cells via suppression transforming growth factor β-induced epithelial–mesenchymal transition. Neurochemical Research. 2018, 43(3), 760–774. https://doi.org/10.1007/s11064-018-2478-y




How to Cite

SOUZA, A.A. de M.., GERVÁSIO, E.R.., DE PAULA, T.B.., DA SILVA NETO, L.R., FERNANDES, F.P.C.., LEITE, G.F.., BARRETO , F.P.. and RIBEIRO , R.I.M. de A., 2021. Effects of Stryphnodendron adstringens extracts on murine 4T1 tumor line. Bioscience Journal [online], vol. 37, pp. e37055. [Accessed22 February 2024]. DOI 10.14393/BJ-v37n0a2021-50347. Available from: https://seer.ufu.br/index.php/biosciencejournal/article/view/50347.



Biological Sciences