Spinochrome D Attenuates Doxorubicin-Induced Cardiomyocyte Death via Improving Glutathione Metabolism and Attenuating Oxidative Stress.

Doxorubicin, an anthracycline from Streptomyces peucetius, exhibits antitumor activity against various cancers. However, doxorubicin is cardiotoxic at cumulative doses, causing increases in intracellular reactive oxygen species in the heart. Spinochrome D (SpD) has a structure of 2,3,5,6,8-pentahydroxy-1,4-naphthoquinone and is a structural analogue of well-known sea urchin pigment echinochrome A. We previously reported that echinochrome A is cardioprotective against doxorubicin toxicity. In the present study, we assessed the cardioprotective effects of SpD against doxorubicin and determined the underlying mechanism. ¹H-NMR-based metabolomics and mass spectrometry-based proteomics were utilized to characterize the metabolites and proteins induced by SpD in a human cardiomyocyte cell line (AC16) and human breast cancer cell line (MCF-7). Multivariate analyses identified 12 discriminating metabolites (variable importance in projection > 1.0) and 1814 proteins from SpD-treated AC16 cells. Proteomics and metabolomics analyses showed that glutathione metabolism was significantly influenced by SpD treatment in AC16 cells. SpD treatment increased ATP production and the oxygen consumption rate in D-galactose-treated AC16 cells. SpD protected AC16 cells from doxorubicin cytotoxicity, but it did not affect the anticancer properties. With SpD treatment, the mitochondrial membrane potential and mitochondrial calcium localization were significantly different between cardiomyocytes and cancer cell lines. Our findings suggest that SpD could be cardioprotective against the cytotoxicity of doxorubicin.

Comparative stability of dimeric and monomeric pigments extracted from sea urchin Strongylocentrotus droebachiensis.

Ultraviolet-visible spectroscopy and UPLC-DAD-MS were used for analysis of stability of ethanol solutions of ethylidene-6,6'-bis(2,3,7-trihydroxynaphthazarin) (ENZ), spinochrome dimer (SDM) and spinochrome D (SD) that were isolated from Strongylocentrotus droebachiensis. In the freshly prepared solution, the concentration of ENZ at pH 6.0 was at 6 fold less comparing to pH 1.6. The increase of pH up to 4.0 resulted to increase of SD concentration and to decrease of SDM concentration. After 48 h storage, both dimers showed the highest stability at pH 1.6, while the elevation of the pH solution up to 6.0 activates degradation of SDM and ENZ at 1.3 and 3.6 fold correspondingly. The concentration of SD after 48 h storage at the pH 1.6 was at two-fold less comparing to the initial concentration, and at the pH 6.0 - at 4 fold less. This study contributes to increasing the knowledge on the stability of the spinochrome pigments.