Nano-chemotherapeutic efficacy of (-) -epigallocatechin 3-gallate mediating apoptosis in A549 cells: Involvement of reactive oxygen species mediated Nrf2/Keap1 signaling

Chemotherapeutic drugs exert systemic toxicity in lung cancer cells and therefore novel treatment strategies are warranted. Epigallocatechin 3-gallate (EGCG), though possessing beneficial effects in alleviating cancer, its effect has been limited due to ineffective systemic delivery, toxicity and bioavailability. To attain the maximum therapeutic response of EGCG, we have synthesized bovine serum albumin (BSA) encapsulated magnetite nanoparticle (MNPs) loaded with EGCG (nano EGCG). The synthesized nano EGCG was characterized using HR-TEM, XRD and FT-IR. Cytotoxicity analysis of BSA-MNP and nano EGCG using flow cytometry was evaluated in lung adenocarcinoma A549 cells. The effect of native and nano EGCG modulating apoptosis and Nrf2/Keap1 signaling was analysed. Nano EGCG exhibited increased ROS/RNS levels and decreased mitochondrial membrane potential, as evaluated by DCFH and JC1 staining, respectively. Expression of pro-apoptotic Bcl-2 family proteins (Bcl-2, Bax, Bak, Bim and Puma) was evaluated. This study demonstrates that native and nano EGCG induces apoptosis through the involvement of ROS leading to loss in mitochondrial membrane potential. EGCG exhibited an increased expression of Nrf2 and Keap1 that could regulate apoptosis in A549 cells. This study, for the first time reveals the potential of BSA-MNPs loaded EGCG as drug target and renders better efficacy against lung cancer cells. (C) 2018 Elsevier Inc. All rights reserved.