Low dose epigallocatechin‐3‐gallate revives doxorubicin responsiveness by a redox‐sensitive pathway in A549 lung adenocarcinoma cells
Suchisnigdha Datta, Dona Sinha
Abstract
Pulmonary cancer confronts the greatest hurdle of resistance against most chemotherapeutic drugs. This may be circumvented with a combination of conventional chemotherapy with bioactive herbal adjuvant. Epigallocatechin-3-gallate (EGCG), was investigated for its chemo-sensitizing property along with doxorubicin (Dox), in an intrinsically nonresponsive lung adenocarcinoma (LAC) cell line, A549. A compromised functionality of Dox was reversed when EGCG was used as an adjuvant. On one hand, Dox (10 μM)-EGCG (0.5 μM) post treatment combination decreased the drug efflux, multidrug-resistance (MDR) signaling, invasiveness while, on the other hand, it increased drug internalization, cell-cycle arrest, stress-induced damage, and finally cell death. The resistant nature of A549 was probably due to constitutive activation of nuclear erythroid 2-related factor 2 (Nrf2) and its upstream/downstream antioxidant effectors, which were also pro-oxidatively coordinated by EGCG. In conclusion low dose EGCG improved Dox-toxicity and imparted oxidative damage-mediated antineoplastic efficacy by reorienting the redox signaling in A549 LAC cells.