Generic placeholder image

Current Nutrition & Food Science

Editor-in-Chief

ISSN (Print): 1573-4013
ISSN (Online): 2212-3881

Research Article

Orally Administered Curcumin Inhibits Breast Cancer In vivo and Reduces Cell Proliferation In vitro in an Iron Dependent Manner

Author(s): Marce Inzunza-Soto, Emir Leal-León, Marcela Vergara-Jiménez, Samuel López-Moreno, Dora Maria Cedano-Prieto, Moises Franco, Jesús Enrique Jiménez-Ferrer, Elian Yuritzi Alegría Herrera, Jonathan Cortés Alvarez, David Alemán-Hidalgo and Eli Teran-Cabanillas*

Volume 19, Issue 4, 2023

Published on: 21 October, 2022

Page: [461 - 468] Pages: 8

DOI: 10.2174/1573401318666220908122614

Price: $65

Abstract

Background: Increased intracellular iron metabolism is a hallmark of breast cancer. Curcumin is an iron chelator with suggested anti-proliferative effects in breast cancer cell lines. However, preclinical studies in murine models are required to validate these important benefits.

Aims: Therefore, this study aimed to determine if the iron-chelating properties of curcumin are responsible for its anti-proliferative effect in breast cancer cells and to investigate the translation of this effect to in vivo models.

Methods: For in vitro experiments, human MCF-7 and mouse 4T1 breast cancer cells were tested. Cell proliferation was assessed in the presence and absence of different concentrations of FAC (ferric ammonium citrate) and curcumin. For in vivo studies, 4T1 cells were implanted into BALB/c mice. After tumor development, animals were divided into four groups (n=5); control, curcumin, optimized curcumin (OC) and chemotherapy group. Tumor volumes were calculated prior and posterior oral gavage treatments.

Result: Curcumin inhibited cell proliferation in both MCF-7 and 4T1 cell lines in a seemingly iron-dependent manner. FAC addition inhibited the anti-proliferative effect exhibited by curcumin. Moreover, curcumin group showed a significantly decreased in tumor growth; interestingly, treatment with OC supplement induced the opposite effect.

Conclusion: These results suggest that curcumin may have an important positive impact on breast cancer, due to its iron-dependent and anti-proliferative properties.

Keywords: Breast cancer, iron, curcumin, MCF-7, 4T1, obesity.

Graphical Abstract
[1]
Naja F, Nasreddine L, Awada S, El Sayed Ahmad R, Hwalla N. Nutrition in the prevention of breast cancer: a middle eastern perspective. Front Public Health 2019; 7: 316.
[http://dx.doi.org/10.3389/fpubh.2019.00316] [PMID: 31788465]
[2]
International Agency for Research on Cancer. Latest global cancer data: cancer burden rises to 18.1 million new cases and 9.6 million cancer deaths. 2018. Available from: https://www.iarc.who.int/wp-content/uploads/2018/09/pr263_E.pdf [Accessed on: 2019 December 15].
[3]
Watkins EJ. Overview of breast cancer. JAAPA 2019; 32(10): 13-7.
[http://dx.doi.org/10.1097/01.JAA.0000580524.95733.3d] [PMID: 31513033]
[4]
Merino BJA, Torres TM, Ros MLH. El cáncer de mama en el siglo XXI: de la detección precoz a los nuevos tratamientos. Radiologia 2017; 59(5): 368-79.
[http://dx.doi.org/10.1016/j.rx.2017.06.003]
[5]
Wallace TC, Bultman S, D’Adamo C, et al. Personalized nutrition in disrupting cancer proceedings from the 2017 american college of nutrition annual meeting. J Am Coll Nutr 2019; 38(1): 1-14.
[6]
Monroy Cisneros K, Astiazarán García H, Esparza Romero J, et al. Impacto del tratamiento antineoplásico en el estado nutricional en pacientes con cáncer de mama. Nutr Hosp 2014; 30(4): 876-82.
[PMID: 25335676]
[7]
Chekhun VF, Lukyanova NY, Burlaka AP, et al. Iron metabolism disturbances in the MCF-7 human breast cancer cells with acquired resistance to doxorubicin and cisplatin. Int J Oncol 2013; 43(5): 1481-6.
[http://dx.doi.org/10.3892/ijo.2013.2063] [PMID: 23969999]
[8]
Brown RAM, Richardson KL, Kabir TD, Trinder D, Ganss R, Leedman PJ. Altered iron metabolism and impact in cancer biology, metastasis and immunology. Front Oncol 2020; 10: 476.
[http://dx.doi.org/10.3389/fonc.2020.00476] [PMID: 32328462]
[9]
Torti SV, Torti FM. Cellular iron metabolism in prognosis and therapy of breast cancer. Crit Rev Oncog 2013; 18(5): 435-48.
[http://dx.doi.org/10.1615/CritRevOncog.2013007784] [PMID: 23879588]
[10]
Zhang S, Chen Y, Guo W, et al. Disordered hepcidin–ferroportin signaling promotes breast cancer growth. Cell Signal 2014; 26(11): 2539-50.
[http://dx.doi.org/10.1016/j.cellsig.2014.07.029] [PMID: 25093806]
[11]
Jung M, Mertens C, Tomat E, Brüne B. Iron as a central player and promising target in cancer progression. Int J Mol Sci 2019; 20(2): 273.
[http://dx.doi.org/10.3390/ijms20020273] [PMID: 30641920]
[12]
Pfeifhofer-Obermair C, Tymoszuk P, Petzer V, Weiss G, Nairz M. Iron in the tumor microenvironment-connecting the dots. Front Oncol 2018; 8: 549.
[http://dx.doi.org/10.3389/fonc.2018.00549] [PMID: 30534534]
[13]
Torti SV, Torti FM. Iron and cancer: More ore to be mined. Nat Rev Cancer 2013; 13(5): 342-55.
[http://dx.doi.org/10.1038/nrc3495] [PMID: 23594855]
[14]
Lv ZD, Liu XP, Zhao WJ, et al. Curcumin induces apoptosis in breast cancer cells and inhibits tumor growth in vitro and in vivo. Int J Clin Exp Pathol 2014; 7(6): 2818-24.
[PMID: 25031701]
[15]
Lin M, Teng L, Wang Y, Zhang J, Sun X. Curcumin-guided nanotherapy: A lipid-based nanomedicine for targeted drug delivery in breast cancer therapy. Drug Deliv 2016; 23(4): 1420-5.
[http://dx.doi.org/10.3109/10717544.2015.1066902] [PMID: 26203688]
[16]
Yang C, Ma X, Wang Z, et al. Curcumin induces apoptosis and protective autophagy in castration-resistant prostate cancer cells through iron chelation. Drug Des Devel Ther 2017; 11: 431-9.
[http://dx.doi.org/10.2147/DDDT.S126964] [PMID: 28243065]
[17]
Moghtaderi H, Sepehri H, Attari F. Combination of arabinogalactan and curcumin induces apoptosis in breast cancer cells in vitro and inhibits tumor growth via overexpression of p53 level in vivo. Biomed Pharmacother 2017; 88: 582-94.
[http://dx.doi.org/10.1016/j.biopha.2017.01.072] [PMID: 28152473]
[18]
Bayet-Robert M, Kwiatowski F, Leheurteur M, et al. Phase I dose escalation trial of docetaxel plus curcumin in patients with advanced and metastatic breast cancer. Cancer Biol Ther 2010; 9(1): 8-14.
[http://dx.doi.org/10.4161/cbt.9.1.10392] [PMID: 19901561]
[19]
Kunnumakkara AB, Bordoloi D, Padmavathi G, et al. Curcumin, the golden nutraceutical: Multitargeting for multiple chronic diseases. Br J Pharmacol 2017; 174(11): 1325-48.
[http://dx.doi.org/10.1111/bph.13621] [PMID: 27638428]
[20]
Laboratoire Optim. Optim curcuma - suplemento de curcumina Longvida. 2019. Available from: https://www.laboratoire-optim.es/optim-curcuma/ [Accessed on: 2020 Junary 19].
[21]
Bernabé-Pineda M, Ramírez-Silva MT, Romero-Romo MA, González-Vergara E, Rojas-Hernández A. Spectrophotometric and electrochemical determination of the formation constants of the complexes Curcumin–Fe(III)–water and Curcumin–Fe(II)–water. Spectrochim Acta A Mol Biomol Spectrosc 2004; 60(5): 1105-13.
[http://dx.doi.org/10.1016/S1386-1425(03)00344-5] [PMID: 15084330]
[22]
García-Quiroz J, García-Becerra R, Santos-Cuevas C, et al. Synergistic antitumorigenic activity of calcitriol with curcumin or resveratrol is mediated by angiogenesis inhibition in triple negative breast cancer xenografts. Cancers 2019; 11(11): 1739.
[http://dx.doi.org/10.3390/cancers11111739] [PMID: 31698751]
[23]
Gota VS, Maru GB, Soni TG, Gandhi TR, Kochar N, Agarwal MG. Safety and pharmacokinetics of a solid lipid curcumin particle formulation in osteosarcoma patients and healthy volunteers. J Agric Food Chem 2010; 58(4): 2095-9.
[http://dx.doi.org/10.1021/jf9024807] [PMID: 20092313]
[24]
Joint FAO/WHO Expert Committee on Food Additives. Curcumin: chemical and technical assessment (CTA) first draft prepared by Ivan Stankovic. 2003. Available from: https://www.fao.org/documents/card/es/c/d63e86e5-f354-4588-b402-b886784b9079/ [Accessed on: 2020 March 21].
[25]
European Food Safety Authority. Refined exposure assessment for curcumin (E 100). EFSA J 2014; 12(10): 3876.
[http://dx.doi.org/10.2903/j.efsa.2014.3876]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy