Study on the precise mechanism of Mitoxantrone-induced Jurkat cell apoptosis using surface enhanced Raman scattering

Mitoxantrone (MTX), one representative of anthraquinone ring anticancer drugs, reveals excellent anticancer effects in acute leukemia. Though current studies have shown that MTX-induced acute leukemia cell apoptosis is implemented by inserting into DNA, and then leading to DNA breakage and the subsequent transcription termination, but the specific location information of MTX embedded in DNA remains unknown. In this study, combining surface enhanced Raman scattering (SERS) and principal component analysis (PCA), we achieve the biochemical changes of MTX-induced Jurkat cell apoptosis and the location information of MTX embedded in DNA. In contrast, we also present the corresponding result of Daunorubicin (DNR)-induced Jurkat cell apoptosis. It is found that the location of MTX embedded in DNA of Jurkat cell is different from DNR, in which the action site of MTX is mainly implemented by blocking and destroying AT base pairs while DNR is performed by embedding and destroying GC base pairs and then the base A. Clearly, this achieved information is very useful for the designing and modification of anthraquinone ring anticancer drugs. Based on surface-enhanced Raman spectroscopy, the biochemical changes of MTX-induced Jurkat cell apoptosis and the location information of MTX embedded in DNA are achieved. MTX is implemented by destroying the phosphoric acid two ester bonds and breaking the DNA phosphate backbone, and the AT base pairs are embedded and the hydrogen bonds in base pairs are destroyed, thus resulting in the dissociation of a large number of base A and subsequent aggregation. In contrast, in addition to destroying the phosphoric acid skeleton and hydrogen bond, DNR mainly acted on GC base pairs, which also can destroy a few of base A and lead to in the free and subsequent aggregation of a large number of base C and a few of base A. [Display omitted] •In this study, combining surface-enhanced Raman spectroscopy, UV-Vis absorption spectroscopy and fluorescence imaging, we achieve the biochemical changes of MTX-induced Jurkat cell apoptosis and the location information of MTX embedded in DNA by first time.•In this study, we first found that although the main action of MTX and DNR-induced Jurkat cell performed in DNA, their action sites are not same.•This experiment is the first to explore the reaction groups of MTX and DNR in the process of inducing DNA fragmentation.