Gambogic acid and chloroquine synergistically induce cell death via increasing mitochondria damage in human NSCLC cells

Abstract

AbstractGambogic acid is a natural bioactive compound from the brownish resin of the Garcinia hanburyi trees, which has been shown to induce cell death of cancer cells with a synergistic effect together with other compounds. In the present study, we aim to investigate whether the combination of gambogic and chloroquine, one of the inhibitor of autophagy, could increase cell death in human NSCLC cells. As a result, gambogic acid and chloroquine synergistically suppress the growth of NSCLC cells (CI <0.9). Moreover, the combination of gambogic acid and chloroquine significantly promotes apoptosis than that either alone does. Mechanistically, the results demonstrate that gambogic acid increases PINK1 expression at mRNA and protein level, accompanied with downregulation of Tom20, suggesting the mitophagy process is activated. Both silencing PINK1 and treatment of chloroquine could inhibit mitophagy, therefore disrupting the clearance of damaged mitochondria. Thus, co‐treatment of gambogic acid and chloroquine results in an elevated level of ROS, which facilitates cell death. Taken together, our finding highlights that the synergistically inhibitory effect of gambogic acid and chloroquine on NSCLC cells is associated with the accumulation of mitochondrial damage.