Naringenin inhibits migration of breast cancer cells via inflammatory and apoptosis cell signaling pathways
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Naringenin, a flavonoid compound, has a wide variety of uses in the pharmaceutical industry for its antioxidant and anti-inflammatory potential.
The current experiment aimed to investigate the anticancer effect of naringenin in triple-negative human breast cancer cells (MDA-MR-231) and an animal model with 7,12-dimethylbenz[a] anthracene (DMBA)-induced breast cancer in female rats to determine the mechanisms and molecular targets.
The cytotoxic effects of naringenin against MDA-MB-231 cells were assessed by MTT assay. Apoptosis and cell cycle alterations were analyzed via flow cytometry. Morphological and biochemical changes in DMBA-induced cancer with naringenin treatment were assayed using our protocol. The potential mechanisms of action were verified via qRT-PCR.
Naringenin was found to inhibit cell proliferation in a time- and concentration-dependent manner. This effect was associated with cell cycle arrest at the G0/G1 phase, along with apoptosis and deposition at the sub-G1 phase (75%). Treatment with naringenin reduced tumor incidence (45.55, 40, and 27.67%) and tumor burden (78.7, 35.4, and 1.2 g) in a dose-dependent manner. Naringenin treatment altered the biochemical and antioxidant parameters related to inflammation necessary for anticancer activity. The qRT-PCR studies further confirmed the mitochondrial-mediated apoptotic effects of naringenin.
On the basis of these results, we can conclude that naringenin exerts an anticancer effect in the MDA-MB-231 cell line that arrests cell development at the G0/G1 phase, and in vivo it alters the mitochondrial-mediated intrinsic pathway responsible for apoptosis.
KeywordsNaringenin Apoptosis Caspase-3 DMBA Breast cancer
- Jagadeesan AJ, Langeswaran K, Gowtham Kumar S et al (2013) Chemopreventive potential of diosgenin on modulating glycoproteins, TCA cycle enzymes, carbohydrate metabolising enzymes and biotransformation enzymes against N-methyl-N-nitrosourea induced mammary carcinogenesis. Int J Pharm Pharm Sci 5(4):575–582Google Scholar
- Jiang XJ, Wang XD (2004) Cytochrome C-mediated apoptosis. Annu Rev Biochem. https://doi.org/10.1146/annurev.biochem.73.011303.073706 Google Scholar
- Kumar V, Bhatt PC, Rahman M, Kaithwas G, Choudhry H, Al-Abbasi FA, Anwar F, Verma A (2017) Fabrication, optimization, and characterization of umbelliferone β-Dgalactopyranosideloaded PLGA nanoparticles in treatment of hepatocellular carcinoma: in vitro and in vivo studies. Int J Nanomed 12:6747–6758CrossRefGoogle Scholar
- Mehta RG (2000) Experimental basis for the prevention of breast cancer. In: European Journal of CancerGoogle Scholar
- Panebianco C, Eddine FBN, Forlani G, Palmieri G, Tatangelo L, Villani A, Xu L, Accolla R, Pazienza V (2018) Probiotic Bifidobacterium lactis, anti-oxidant vitamin E/C and anti-inflammatory dha attenuate lung inflammation due to pm2.5 exposure in mice. Benef Microb 10:1–8Google Scholar
- Papadakis KA, Abreu MT (2006) Systemic consequences of intestinal inflammation. In: Targan SR, Shanahan F, Karp LC (eds) Inflammatory bowel disease: from bench to bedside. Springer, Boston, MA. https://doi.org/10.1007/0-387-25808-6_12
- Sakthivel KM, Chandrasekaran G (2014) Protective effect of acacia ferruginea against ulcerative colitis via modulating inflammatory mediators, cytokine profile and NF-κB signal transduction pathways. J Environ Pathol Toxicol Oncol. https://doi.org/10.1615/JEnvironPatholToxicolOncol.2014008425 Google Scholar
- Tamarkin L, Cohen M, Reichert C et al (1981) Melatonin inhibition and pinealectomy enhancement of 7,12-dimethylbenz(a)anthracene-induced mammary tumors in the rat. Cancer Res 41(11 Pt 1):4432–4436Google Scholar