Graphene oxide-chloroquine conjugate induces DNA damage in A549 lung cancer cells through autophagy modulation.

Abstract

Autophagy is a highly regulated catabolic process by which unnecessary, dysfunctional, or damaged proteins and other cellular components are degraded and recycled to promote cellular differentiation, survival, and development. In response to endogenous or exogenous stresses, cancer cells use autophagy pathways for survival through activation of complex DNA damage repair (DDR) mechanisms. In the present study, we demonstrated the genotoxicity induced in A549 lung cancer cells by exposure to the GO-Chl nanoconjugate and elucidated the role of autophagy modulation in harnessing the DNA-damage response. GO-Chl causes loss of plasma membrane integrity, cell cycle arrest, and significant genotoxicity in A549 cells. Further, elevated expression of key autophagy proteins beclin-1, ATG-7, LC-3-I/II, and SQSTM1/p62 reveal that inhibition of autophagy plays a crucial role in regulating DDR capabilities of cancer cells. The results indicate that the interplay between DDR and autophagy pathways may open new paradigms for developing effective combinatorial nanoscale drug systems against multidrug-resistance cancers.