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ORIGINAL ARTICLE
Year : 2018  |  Volume : 14  |  Issue : 55  |  Page : 110-117

Taxifolin possesses anti-cancer activity on the 7,12-Dimethylbenz(a)anthracene-Induced breast cancer in the sprague dawley rats by remodeling nuclear factor Erythroid 2- Kelch-Like ECH-Associated Protein 1-Heme Oxygenase 1 and anti-oxidant pathways


1 Department of Pharmaceutical Sciences and Technology, Division of Advanced Pharmacology, BIT Mesra, Ranchi, Jharkhand, India
2 Department of Pharmaceutical Sciences and Technology, Division of Pharmaceutical Chemistry, BIT Mesra, Ranchi, Jharkhand, India

Correspondence Address:
Shakti Prasad Pattanayak
Department of Pharmaceutical Sciences and Technology, Division of Advanced Pharmacology, BIT Mesra, Ranchi - 835 215, Jharkhand
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/pm.pm_601_17

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Background: In mammary cancer, alterations in various gene expressions and signaling pathways occurs due to the secondary effects of oxidative stress that facilitates cancer by causing genomic instability and mutagenic alterations. Several phenolic compounds are active against various malignancies. Taxifolin (TAX) exhibits diverse bioactivity profile that also contributes toward its anticancer efficacy. Objective: The present study has been designed for estimation of the anticancer potential of TAX on 7,12-dimethylbenz(a)anthracene (DMBA)-induced breast cancer in Sprague Dawley (SD) rats. Materials and Methods: Molecular docking analysis of Kelch-like ECH-associated protein 1 (Keap-1) and heme oxygenase-1 (HO-1) was carried out using Maestro tool to rationalize the activity of TAX based on their binding potential. This was followed by DMBA administration in air pouch to induce mammary cancer in female SD rats (50–55 days old). After 90 days of cancer induction, the chemotherapeutic potential of TAX was evaluated by the administration of TAX at doses 10, 20, and 40 mg/kg/day. Besides this, the effect of TAX on Keap-1-nuclear factor erythroid-2 (Nrf-2) pathway associated with HO-1 and NADPH:quinoneoxidoreductase 1 (NQO1) expressions and their effect on the anti-oxidative and anti-proliferative activity was also evaluated through immunofluorescence analysis, real-time quantitative polymerase chain reaction, and biochemical estimations. Results: TAX revealed protective effect against lipid peroxidation, enzymatic (superoxide dismutase [SOD], manganese-containing SOD, copper- and zinc-containing SOD, catalase, and glutathione peroxidase), and nonenzymatic (reduced glutathione, α-tocopherol, and ascorbic acid) anti-oxidative markers in serum, liver, kidney, and breast tissue of both control and experimental groups. The study revealed upregulation of protective Nrf-2, HO-1, and NQO1 expressions with consequent suppression in Keap-1 mRNA expression. Conclusion: This study revealed the potency of TAX in the inhibition of mammary carcinogenesis through Nrf-2-Keap-1-HO-1 and antioxidant pathway. Abbreviations used: RT-qPCR: Real-time quantitative polymerase chain reaction; ODC: Ornithin decarboxylase; HO-1; Heme oxygenase-1; PAHs: Polyaromatic hydrocarbons; TBARS: Thiobarbituric acid reactive species; NQO1: NADPH:quinoneoxidoreductase 1; Keap-1: Kelch-like ECH associated protein 1; Nrf2: Nuclear factor erythroid 2; SD: Sprague Dawley.


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