GO-Chl induce DNA damage in A549 lung cancer cells through SQSTM1/p62 mediated autophagy modulation

Autophagy, a highly regulated catabolism for the degradation of unnecessary or dysfunctional cellular proteins. In response to endogenous or exogenous stresses the cancer cells use autophagy pathways for their survival through activation of complex DNA damage repair (DDR) mechanism. In the present study, we have 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, LC3- I/II and SQSTM1/p62 reveal that inhibition of autophagy plays a crucial role in regulating the DDR capabilities of cancer cells. The results indicate that the interplay of DDR and autophagy pathways may open new paradigms for developing effective combinatorial nanodrug system against multidrug resistance cancers.