The Mechansim Of Shikonin-induced Apoptosis In MCF-7Breast Cancer

Shikonin is one of major compounds existing in the root of Lithospermumerythrorhizon. Despite shikionin was shown to induce apoptosis in several tumor cells,including MCF-7, the molecular mechanism responsible remains elusive.We found that the inhibitory rate increased significantly and morphologychanging clearly after shikonin treatment by using MTS assay and light microscopy,indicating that the inhibitory degree is time and dose-dependent. Furthermore, weused AO-EB staining assay and agarose gel electrophoresis to determine the cellapoptosis. Our data showed that shikonin treatment caused chromatin condensation ofMCF-7cell and the ladder pattern of internucleosomal cleavage characteristic ofapoptosis, confirming shikonin can directly induce MCF-7cell apoptosis at thecellular and molecular levels. Finally, we showed that shikonin treatment induceddown-regulation of Bcl-2and p-Drp1and up-regulation of Bax, GRP78, XBP-1andDrp1; moreover, shikonin treatment increased the activity of caspase-3in MCF-7cells significantly.This study suggests that endoplasmic reticulum stress, mitochondrial pathwayand caspase-3are involved in apoptotic process of MCF-7cells.