Fabrication and characterization of solid lipid nano-formulation of astraxanthin against DMBA-induced breast cancer via Nrf-2-Keap1 and NF-kB and mTOR/Maf-1/PTEN pathway

• Published in: Drug delivery Vol. 26; no. 1; pp. 975 - 988
• Main Authors: Sun, Tao, Gao, Jun, Han, Dan, Shi, Hongyan, Liu, Xianqiang
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 01.01.2019; Taylor & Francis Ltd; Taylor & Francis Group
• Subjects: Animals; Anthracenes - pharmacology; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - chemical synthesis; antioxidant; Astraxanthin; Bioavailability; Breast cancer; Breast Neoplasms - chemically induced; Breast Neoplasms - drug therapy; Cancer therapies; Drug delivery systems; Drugs; Enzymes; Female; HMG-CoAR; Humans; Keap1; Kelch-Like ECH-Associated Protein 1 - metabolism; Lipids; Lipids - chemistry; MCF-7 Cells; metabolizing enzymes; Nanoparticles; Nanoparticles - administration & dosage; Nanoparticles - chemistry; NF-E2-Related Factor 2 - metabolism; NF-kappa B - metabolism; NF-kB; Nrf-2; Particle size; Piperidines - pharmacology; PTEN Phosphohydrolase - metabolism; Rats; Signal Transduction - drug effects; solid lipid nanoparticles; TOR Serine-Threonine Kinases - metabolism; Triglycerides; Tumors; antioxidant; metabolizing enzymes; NF-kB; Nrf-2; solid lipid nanoparticles; Keap1; breast cancer; Astraxanthin; HMG-CoAR
• ISSN: 1071-7544; 1521-0464
• DOI: 10.1080/10717544.2019.1667454

In the current experimental study, we scrutinized the chemoprotective effect of astraxanthin against the 7,12-dimethylbenz(a)anthracene (DMBA)-induced breast cancer via Nrf-2-Keap1 and NF-kB and mTOR/Maf-1/PTEN pathway. The double emulsion solvent displacement method was used for the preparation of astraxanthin solid lipid nanoparticles (SLN). SLNs were appraised for entrapment, potential, size, drug-release performance, and gastric stability. DMBA (8 mg/kg) was used for the induction of breast cancer. Tumor weight, body weight, and tumor incidence were estimated at a regular interval. Different biochemical parameters such as Na+/K+, Ca2+, and Mg2+ activity, antioxidant, lipid, glycoprotein, phase I and II biotransformation enzymes, mitochondrial TCA cycle, and carbohydrate metabolizing enzymes were estimated. Keap1-Nrf-2, associated HO-1, and NF-kB expressions were estimated. Moreover, it estimated the mRNA expression of LXR (α,β), HMG-CoAR, PTEN, Maf1, PI3K, mTOR, Akt, FASN, and ACC1. AX-SLN reduced the tumor incidence, tumor weight, and increased the body weight. AX-SLN exhibited the protective effect against the LPO, enzymic (SOD, CuZnSOD, MnSOD, GPx, and CAT), and nonenzymic (GSH) in the serum, mammary gland, renal, and hepatic tissues. AX-SLN reduced the p-AKT which is accountable for the reduction in the NF-kB expression and also reduced the expression of Keap1 and NF-kB along with increasing the expression of HO-1 and Nrf-2. Further, AX-SLN significantly altered the mRNA of LXR (α,β), HMG-CoAR, PTEN, Maf1, PI3K, mTOR, Akt, FASN, and ACC1. On the basis of the results, we can conclude that AX-SLN inhibits the mammary gland carcinogenesis via Nrf-2-Keap1, NF-kB, and mTOR/Maf-1/PTEN pathway.