A novel synthetic curcumin derivative MHMM-41 induces ROS-mediated apoptosis and migration blocking of human lung cancer cells A549.

Many curcumin derivatives were produced and characterized to improve the physiochemical instability and low solubility of curcumin. Here, MHMM-41 (a novel curcumin derivative) was used to treat non-small lung cancer cells of human (known as A549) and to identify its anti-proliferative activities. Our results suggested that MHMM-41 display no significant cytotoxicity toward normal human lung fibroblast 2BS cells and mouse embryonal fibroblast 3T3 cells. It also had better anti-proliferative activity than curcumin in A549 cells. Further study showed a significant increase of apoptotic A549 cells in time and dose dependent manners. The activation of caspase-3, 8, 9, 12, Bax and PARP proteins were detected. Consequently, MHMM-41 treatment led to the reduction of mitochondrial membrane potential by JC-1 staining and characteristic nuclei fragmentation by Hoechst 33,342 staining, respectively, which showed that A549 apoptosis could be triggered by the extrinsic and intrinsic mitochondrial pathways. The release of ROS was also measured by flow cytometry. Further, wound healing assay and transwell experiments confirmed the anti-migration ability of MHMM-41 in A549 cells. Our current study suggested the potentials of MHMM-41 to inhibit the A549 cell proliferation. However, the intensive mechanical research on the anti-proliferation of A549 cells needs to be performed in the future.