title: Luteolin-loaded phytosomes sensitize human breast carcinoma MDA-MB 231 cells to doxorubicin by suppressing Nrf2 mediated signalling.
abstract: Nuclear factor erythroid 2-related factor 2 (Nrf2) has been recognized as a transcription factor that controls mechanisms of cellular defense response by regulation of three classes of genes, including endogenous antioxidants, phase II detoxifying enzymes and transporters. Previous studies have revealed roles of Nrf2 in resistance to chemotherapeutic agents and high level expression of Nrf2 has been found in many types of cancer. At physiological concentrations, luteolin as a flavonoid compound can inhibit Nrf2 and sensitize cancer cells to chemotherapeutic agents. We reported luteolin loaded in phytosomes as an advanced nanoparticle carrier sensitized MDA-MB 231 cells to doxorubicin. In this study, we prepared nano phytosomes of luteolin to enhance the bioavailability of luteolin and improve passive targeting in breast cancer cells. Our results showed that co- treatment of cells with nano particles containing luteolin and doxorubicin resulted in the highest percentage cell death in MDA-MB 231 cells (p<0.05). Furthermore, luteolin-loaded nanoparticles reduced Nrf2 gene expression at the mRNA level in cells to a greater extent than luteolin alone (p<0.05). Similarly, expression of downstream genes for Nrf2 including Ho1 and MDR1 were reduced significantly (p<0.05). Inhibition of Nrf-2 expression caused a marked increase in cancer cell death (p<0.05). Taken together, these results suggest that phytosome technology can improve the efficacy of chemotherapy by overcoming resistance and enhancing permeability of cancer cells to chemical agents and may thus be considered as a potential delivery system to improve therapeutic protocols for cancer patients.
authors.affiliation: Department of Biochemistry and Clinical Laboratory, Faculty of Medicine, Tabriz University of Medical Sciences, Aras, Tabriz, Iran E-mail : drnsamadi@yahoo.com.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Sabzichi
authors.forename: Hamed
authors.initials: H
authors.lastname: Hamishehkar
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Ramezani
authors.forename: Simin
authors.initials: S
authors.lastname: Sharifi
authors.forename: Maryam
authors.initials: M
authors.lastname: Tabasinezhad
authors.forename: Mohammadbagher
authors.initials: M
authors.lastname: Pirouzpanah
authors.forename: Parisa
authors.initials: P
authors.lastname: Ghanbari
authors.forename: Nasser
authors.initials: N
authors.lastname: Samadi
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001682:Biological Availability; D001943:Breast Neoplasms / Q000188:drug therapy*; D002277:Carcinoma / Q000188:drug therapy*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000494:pharmacology*; D004337:Drug Carriers / Q000008:administration & dosage; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D047311:Luteolin / Q000008:administration & dosage*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D053758:Nanoparticles / Q000008:administration & dosage; D010539:Permeability / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D004317:Doxorubicin; D047311:Luteolin