Abstract
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.
Highlights
Among the common cancers, such as breast, lung, colorectal, and bronchus, breast cancer was diagnosed most commonly among women
The prepared AX-solid lipid nanoparticles (SLN) particles were found in spherical shape with uniform size distribution
Statistical data for the 24 h study showed a higher flux for AX-SLN as compared with that of the control (AX solution) (Supplementary Table 2), whereas the cumulative amount of AX permeated from SLN was 3.75 times higher than that of the control
Summary
Among the common cancers, such as breast, lung, colorectal, and bronchus, breast cancer was diagnosed most commonly among women. The most common risk factors of breast cancer are age, estrogen exposure, mutation in tumor suppressor gene, obesity, and environmental pollutants (Rakha et al, 2007; Li, 2010). Breast cancer is linked with estrogen exposure and age. Steroidal hormones such as estrogen can induce and expand breast cancer. Only two selective estrogen receptor modulators (SERMs) such as raloxifene and tamoxifen were approved from the United States FDA for the treatment of breast cancer in women who are highly susceptible (Brody & Rudel, 2003; Millikan et al, 2008). The effects of these drugs may not completely eliminate the chance of induction of breast cancer; there is a scope for newer interventions (Sutradhar & Amin, 2014)
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